Affinage

CCL25

C-C motif chemokine 25 · UniProt O15444

Length
150 aa
Mass
16.6 kDa
Annotated
2026-04-28
100 papers in source corpus 37 papers cited in narrative 37 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL25 (TECK) is a CC chemokine that functions as the principal ligand for CCR9 to orchestrate lymphocyte trafficking to the thymus and small intestine, governing T-cell development, intestinal intraepithelial lymphocyte maintenance, and IgA-producing cell recruitment. Constitutively produced by thymic epithelial cells and small intestinal crypt epithelium under transcriptional control of Cdx homeodomain proteins and NF-κB, CCL25 binds CCR9 (a Gαi-coupled receptor with two alternatively spliced isoforms that extend the ligand concentration–response range) and also binds the atypical receptor CCX-CKR (PMID:10602049, PMID:10974041, PMID:16517733, PMID:10706668, PMID:10640743, PMID:35782530). Engagement of CCR9 activates PI3K/Akt, p38/ERK MAPK, and Rac/Rap1 GTPase cascades that drive chemotaxis, α4β7-integrin–dependent arrest on MAdCAM-1 under shear flow, α4β1-mediated adhesion to VCAM-1/fibronectin, anti-apoptotic signaling, and CD103-dependent epithelial retention of intraepithelial lymphocytes (PMID:11493434, PMID:17510295, PMID:18308860, PMID:15368288, PMID:20855113). Beyond immune homeostasis, CCL25–CCR9 signaling promotes cancer cell migration and invasion through MMP upregulation and Wnt5a/RhoA pathways, drives osteoclastogenesis via p38/ERK independently of RANKL, and inhibits glucose-stimulated insulin secretion by reducing cAMP in pancreatic islets (PMID:18245522, PMID:21344163, PMID:28380463, PMID:33347617, PMID:33058852).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1997 High

    The discovery of TECK (CCL25) as a thymus-expressed chemokine with chemotactic activity for macrophages, dendritic cells, and thymocytes established the existence of a tissue-restricted chemokine potentially governing thymic cell trafficking.

    Evidence Recombinant protein chemotaxis assay with primary immune cell populations

    PMID:9285413

    Open questions at the time
    • Cognate receptor unknown
    • In vivo role undemonstrated
    • Molecular mechanism of chemotaxis undetermined
  2. 1999 High

    Identification of GPR-9-6 (CCR9) as the specific receptor for CCL25 resolved the signaling entry point, showing exclusive ligand–receptor pairing with calcium mobilization and chemotaxis, and defined CCL25 as active on both immature double-positive and mature single-positive thymocytes.

    Evidence Receptor deorphanization via calcium flux and chemotaxis in CCR9-transfected HEK293 cells; primary human thymocyte migration assays

    PMID:10229797 PMID:10498628

    Open questions at the time
    • In vivo requirement not demonstrated
    • Downstream signaling cascade uncharacterized
    • Additional receptor interactions unknown
  3. 2000 High

    Mapping CCL25 production to thymic epithelial cells and small intestinal crypt epithelium, combined with finding high CCR9 expression on all small intestinal T cells, established the CCL25–CCR9 axis as a dual tissue-homing system for thymus and gut; discovery of CCR9A/B splice variants and CCX-CKR binding expanded the receptor biology.

    Evidence Immunohistochemistry, flow cytometry of tissue lymphocytes, cDNA cloning with dose-response comparison of CCR9 isoforms, radiolabeled ligand binding to CCX-CKR

    PMID:10602049 PMID:10640743 PMID:10706668 PMID:10974041

    Open questions at the time
    • In vivo genetic loss-of-function evidence lacking
    • Functional significance of CCX-CKR binding unclear
    • Transcriptional regulation of CCL25 expression unknown
  4. 2001 High

    Dissection of intracellular signaling revealed that CCL25–CCR9 activates PI3K/Akt (required for chemotaxis) and MAPK pathways, and provides anti-apoptotic survival signals blocking cycloheximide- and partially Fas-mediated cell death, establishing CCL25 as both a migratory and survival factor.

    Evidence Chemical inhibitor studies, phospho-protein immunoblotting, and apoptosis assays (PARP cleavage, caspase-3) in endogenous CCR9-expressing MOLT4 cells

    PMID:11493434

    Open questions at the time
    • GTPase-level effectors for adhesion not identified
    • Survival mechanism in primary cells not confirmed
    • Relative contribution of PI3K vs MAPK to different outcomes unclear
  5. 2002 High

    In vivo studies using antibody neutralization, CCL25-intrakine transgenic mice, and CCR9 expression profiling demonstrated that CCL25 is required for IgA-ASC recruitment to the gut, IEL maintenance and development, cryptopatch formation, and CD8+ T cell homing to the small intestinal epithelium.

    Evidence In vivo anti-CCL25 antibody neutralization in neonatal and adult mice; CCL25-intrakine transgenic model; TCR-transgenic adoptive transfer; sorted ASC chemotaxis assays

    PMID:11751956 PMID:11805153 PMID:12096027 PMID:12393847 PMID:12442331

    Open questions at the time
    • CCL25 complete knockout mouse phenotype not yet reported at this point
    • Redundancy with other gut-homing chemokines not fully delineated
    • Role in thymic progenitor entry not directly tested
  6. 2004 High

    CCL25 was shown to activate α4β7 integrin binding to MAdCAM-1 on hepatic endothelium in primary sclerosing cholangitis, establishing the first ectopic CCL25 disease mechanism, and to promote CD103-mediated IEL adhesion to E-cadherin in a pertussis toxin-sensitive manner, defining an additional integrin-activation pathway.

    Evidence Flow-based adhesion assay on human hepatic endothelium; CCR9−/− adoptive transfer; pertussis toxin treatment with adhesion readout

    PMID:15368288 PMID:15557349

    Open questions at the time
    • Whether ectopic CCL25 expression occurs in other inflammatory liver diseases unclear
    • Signaling intermediates linking CCR9 to CD103 activation not identified
  7. 2006 High

    Transcriptional control of CCL25 was established by showing that Cdx-1 and Cdx-2 homeodomain proteins directly bind the CCL25 promoter to drive its intestinal expression, and functional redundancy with CCL28 was demonstrated for IgA plasmablast recruitment after rotavirus infection.

    Evidence EMSA, promoter-reporter assays, cotransfection in intestinal cell lines; CCR9-KO mice and combined anti-CCL25/anti-CCL28 antibody blockade

    PMID:16517733 PMID:16670280

    Open questions at the time
    • Factors governing thymic CCL25 transcription not identified
    • Whether Cdx regulation is direct in vivo (ChIP-seq) not shown
  8. 2007 High

    The GTPase effector pathway downstream of CCR9 was mapped: CCL25 activates Rac and Rap1 to drive α4β1-integrin adhesion to VCAM-1/fibronectin via WAVE2 and RAPL effectors respectively, and CCL25-KO mice showed that CCL25 is required for gut accumulation but not priming of CCR9-high memory CD8+ T cells.

    Evidence shRNA knockdown of WAVE2/RAPL/RIAM with adhesion assays; CCL25−/− mice with oral antigen sensitization and adoptive transfer

    PMID:17510295 PMID:17548595

    Open questions at the time
    • Whether Rac-WAVE2 and Rap1-RAPL pathways are simultaneously or sequentially engaged unknown
    • Role of CCL25 in memory T cell survival in situ not addressed
  9. 2008 High

    CCL25 was identified as the effector linking androgen withdrawal to enhanced thymic progenitor entry, and was shown to selectively trigger α4β7-dependent (but not α4β1-dependent) lymphocyte arrest under shear flow, while CCR9–CCL25 signaling was found to drive melanoma cell migration and invasion.

    Evidence Castration model with CCL25 antibody blockade and ETP quantification; flow-based adhesion reconstitution with MAdCAM-1/VCAM-1; anti-CCR9 antibody and siRNA in melanoma invasion assays

    PMID:18245522 PMID:18308860 PMID:18694999

    Open questions at the time
    • Mechanism of selectivity for α4β7 over α4β1 under flow not defined
    • In vivo melanoma metastasis not tested with CCL25 perturbation
  10. 2009 High

    CCL25 was integrated into a periodic thymic gating model where its co-expression with P-selectin controls cyclical T-cell progenitor importation, and ezrin was identified as a cytoskeletal scaffold mediating CCL25-induced cell polarization and invasion.

    Evidence Periodic expression analysis with genetic models and competitive TCP reconstitution; miRNA-mediated ezrin silencing with confocal microscopy and invasion assay

    PMID:19289576 PMID:20036004

    Open questions at the time
    • Molecular mechanism linking S1P feedback to CCL25 periodicity not established
    • ERM role confirmed only in MOLT4 cells, not primary lymphocytes
  11. 2010 Medium

    Cancer biology studies extended CCL25–CCR9 survival signaling to prostate cancer (PI3K/Akt/ERK-dependent anti-apoptosis reversed by wortmannin and anti-CCL25 antibodies in xenografts), and the RhoA-ROCK-MLC axis was identified as required for CCL25-driven migration.

    Evidence PI3K inhibitor and in vivo xenograft with CCL25 neutralization; GTPase assays and ROCK inhibitor (Y-27632) in chemotaxis

    PMID:20127861 PMID:20855113

    Open questions at the time
    • Clinical relevance of CCR9-CCL25 axis in prostate cancer not validated in patient cohorts
    • Interplay between RhoA and Rac pathways downstream of CCR9 not resolved
  12. 2011 High

    CCL25 was shown to promote breast cancer invasion through CCR9-dependent upregulation of active MMPs (MMP-1, -9, -11, -13), while CCR9-KO mice revealed a protective role for the CCL25–CCR9 axis in colitis recovery by regulating DC subset balance and limiting Th1/Th17 cytokine production.

    Evidence Migration/invasion assays with anti-CCR9 neutralization and MMP ELISA; DSS colitis in CCR9−/− mice with flow cytometry and cytokine quantification

    PMID:21283540 PMID:21344163

    Open questions at the time
    • Mechanism connecting CCR9 signaling to MMP transcription not defined
    • Whether CCR9-KO colitis phenotype reflects loss of CCL25-responsive regulatory cells specifically not resolved
  13. 2012 High

    Myeloma cells were found to produce CCL25 as a paracrine chemoattractant for bone marrow mesenchymal stromal cells, which in turn enhance myeloma proliferation and survival via AKT/ERK, establishing a CCL25-driven stromal niche feedback loop.

    Evidence CCL25 neutralization in migration and co-culture assays; intrafemoral coengraftment; western blotting

    PMID:22102554

    Open questions at the time
    • Contribution of CCL25 relative to other MSC chemoattractants in myeloma bone marrow not quantified
    • Therapeutic window for CCL25 blockade in myeloma not explored
  14. 2013 High

    A scaffolding mechanism for CCL25-induced drug resistance was defined: phosphorylated ERM proteins link P-glycoprotein to F-actin in T-ALL cells, and ERM silencing disrupts this complex and restores drug sensitivity.

    Evidence Co-immunoprecipitation of p-ERM/P-gp/F-actin; shRNA-mediated ERM knockdown with P-gp functional assay in MOLT4 cells

    PMID:23326330

    Open questions at the time
    • Relevance of ERM-P-gp scaffolding to primary patient T-ALL cells not tested
    • Whether CCL25 directly phosphorylates ERM or acts indirectly not determined
  15. 2017 Medium

    CCL25 was found to induce Wnt5a expression via PKC in T-ALL cells, with Wnt5a then driving migration and invasion through PI3K/Akt-RhoA, revealing a secondary autocrine/paracrine amplification loop for CCL25-induced motility.

    Evidence siRNA and inhibitor knockdowns of PI3K/Akt and RhoA; western blotting for PKC and Wnt5a; confocal and SEM; mouse xenograft

    PMID:28380463

    Open questions at the time
    • Wnt5a induction by CCL25 not confirmed outside MOLT4/T-ALL cells
    • Whether Wnt5a pathway operates in normal thymocyte migration unknown
  16. 2020 High

    An unexpected endocrine role for CCL25 was established: CCL25 acts via Gαi-coupled CCR9 on pancreatic islet cells to inhibit glucose-stimulated insulin secretion by reducing cAMP, an effect blocked by the CCR9 antagonist vercirnon.

    Evidence Insulin secretion, cAMP, and apoptosis assays in primary human and mouse islets with pharmacological CCR9 antagonist

    PMID:33058852

    Open questions at the time
    • In vivo metabolic phenotype of CCL25 or CCR9 deficiency not reported
    • Source of CCL25 reaching islets in vivo not identified
  17. 2021 Medium

    CCL25 was shown to drive inflammatory processes in rheumatoid arthritis by stimulating FLS and monocyte migration via p38/ERK, polarizing monocytes into M1-like macrophages, and inducing osteoclastogenesis through a RANKL-independent, RANK/cathepsin K/TNF-α-dependent mechanism.

    Evidence p38 and ERK inhibitors; osteoclast differentiation assay; cytokine ELISA in RA synovial tissue-derived cells

    PMID:33347617

    Open questions at the time
    • RANKL-independent osteoclastogenesis by CCL25 not confirmed in other systems
    • Therapeutic relevance of CCR9 blockade in RA not tested in vivo
  18. 2022 Medium

    NF-κB was identified as a direct transcriptional regulator of CCL25 in endothelial cells, and CCL25 was shown to increase endothelial permeability by reducing tight junction proteins via P38 MAPK, linking CCL25 to vascular barrier dysfunction.

    Evidence Chromatin immunoprecipitation and luciferase assays for NF-κB binding; TEER and FITC permeability assays; P38 pathway analysis in LPS-stimulated HPMECs

    PMID:35782530

    Open questions at the time
    • In vivo vascular permeability changes from CCL25 not demonstrated
    • Relationship between NF-κB-driven endothelial CCL25 and Cdx-driven intestinal CCL25 not explored

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of CCL25–CCR9 interaction and selective integrin activation, the full physiological consequence of CCX-CKR/ACKR4 scavenging of CCL25, the in vivo metabolic impact of islet CCR9 signaling, and whether CCL25-targeted therapies (e.g., vercirnon) can selectively modulate gut homing without compromising thymic function.
  • No structural model of CCL25–CCR9 complex
  • CCX-CKR/ACKR4 functional role in CCL25 gradient shaping not established in vivo
  • Tissue-specific therapeutic targeting strategies untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 6 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 5
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 6 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 3
Partners
ACKR4CCR9EZRITGA4ITGB1ITGB7MADCAM1

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 CCL25 (TECK) is produced by thymic dendritic cells and exhibits chemotactic activity for activated macrophages, dendritic cells, and thymocytes in vitro. Recombinant protein chemotaxis assay; source identification by cell-type-specific expression analysis Immunity High 9285413
1999 CCL25 binds specifically to the orphan receptor GPR-9-6 (renamed CCR9), inducing intracellular calcium mobilization and in vitro migration of CCR9-transfected cells; no other chemokines tested produced responses via CCR9. Calcium flux assay and chemotaxis assay in CCR9-transfected HEK293 cells Journal of immunology High 10229797 10498628
1999 CCL25 (TECK) efficaciously induces chemotaxis of immature CD4+CD8+ double-positive and mature CD4+ and CD8+ single-positive human thymocytes via CCR9. In vitro chemotaxis assay with primary human thymocytes and CCR9-expressing cell lines Blood High 10498628
2000 CCL25 is produced predominantly by thymic epithelial cells (not dendritic cells) and by small intestinal epithelial cells; it chemoattracts both double-positive and single-positive thymocytes via CCR9. Immunohistochemistry and in vitro migration assays; CCR9 cDNA cloning and localization European journal of immunology High 10602049
2000 CCR9 is expressed at high levels on essentially all small intestinal CD4+ and CD8+ T lymphocytes, and CCL25 is expressed selectively by small intestinal crypt epithelium; this CCL25–CCR9 axis mediates selective migration of lymphocytes to the small intestinal mucosa. Immunohistochemistry; in vitro migration assay; flow cytometry of tissue lymphocytes The Journal of experimental medicine High 10974041
2000 CCL25 also binds with high affinity to CCX-CKR (provisionally CCR10), a second chemokine receptor, with IC50 <15 nM, as determined by stalkokine adhesion and radiolabeled ligand competition assays. Stalkokine adhesion assay; radiolabeled ligand binding and competition with >80 chemokines Journal of immunology High 10706668
2000 CCR9 exists as two alternatively spliced isoforms, CCR9A (12 extra N-terminal amino acids) and CCR9B; CCR9A has a lower EC50 for CCL25 and is desensitized at doses that do not silence CCR9B, extending the concentration range over which cells respond to CCL25. cDNA cloning, calcium flux assay and chemotaxis assay comparing CCR9A vs CCR9B transfectants Journal of immunology High 10640743
2001 CCR9 engagement by CCL25 activates PI3K-dependent phosphorylation of Akt, GSK-3β, and FKHR, and MAPK; PI3K (but not MAPK) is required for CCR9-mediated chemotaxis. CCL25/CCR9 signaling provides a cell survival signal blocking cycloheximide-induced and partially Fas-mediated apoptosis independently of c-FLIPL. Chemical inhibitor studies, immunoblotting for phosphorylated proteins, apoptosis assays (PARP cleavage, caspase-3 activation) in MOLT4 cells naturally expressing CCR9 Blood High 11493434
2002 CCL25 selectively chemoattracts IgA antibody-secreting cells (ASC) from spleen, Peyer's patches, and mesenteric lymph nodes via CCR9; IgG- and IgM-ASC respond poorly. Small intestinal epithelial cells selectively express CCL25, consistent with targeting IgA-producing cells to the gut wall. In vitro migration/chemotaxis assays with sorted antibody-secreting cells; immunohistochemistry The Journal of experimental medicine High 11805153
2002 CCR9 expression is maintained on CD8αβ+ T cells activated in mesenteric lymph nodes but rapidly downregulated on those activated in peripheral lymph nodes; in vivo neutralization of CCL25 reduced the ability of CCR9+ CD8αβ+ lymphocytes to populate the small-intestinal epithelium. TCR transgenic T cell transfer model; in vivo antibody neutralization; flow cytometry The Journal of clinical investigation High 12393847
2002 CCL25–CCR9 signaling is essential for cryptopatch (CP) formation in the gut and the consequent thymus-independent generation of intestinal intraepithelial T lymphocytes (IEL); CD11c+ dendritic stromal cells in CPs express CCL25, and c-kit+ Lin− bone marrow progenitors express CCR9 and migrate in response to CCL25. CCL25 intrakine transgenic mice (dominant-negative CCL25 signaling); bone marrow reconstitution; RT-PCR; chemotaxis assay International immunology High 12096027
2002 Anti-CCL25 antibody administration to neonatal mice reduces CD8αα+TCRγδ+ and CD8αα+TCRαβ+ IEL by ~50%, demonstrating CCL25 is required for maintenance/development of IEL precursors in the small intestine. In vivo antibody neutralization in neonatal mice; flow cytometry; CCR9 expression analysis on IEL precursors European journal of immunology High 12442331
2002 CCR9 is expressed on the majority of CD4+CD8+ double-positive thymocytes but not on CD4−CD8− double-negative thymocytes; CD69+ thymocytes show enhanced CCL25-induced migration compared to CD69− thymocytes; TCR stimulation augments CCL25 responsiveness; ~50% of γδTCR+ thymocytes and peripheral γδ T cells express CCR9 and migrate in response to CCL25. Polyclonal anti-CCR9 antibody generation; flow cytometry; in vitro migration assays of sorted thymocyte subpopulations Journal of immunology High 11751956
2003 CCL25/CCR9-mediated lymphocyte adhesion to small intestinal microvessels is demonstrated in vivo; CCR9 desensitization or anti-CCL25 antibody significantly inhibits LPL adhesion in small (but not large) intestine, including TNF-α-induced adhesion; TNF-α upregulates CCL25 expression in small intestinal lamina propria. Intravital microscopy; in vivo CCR9 desensitization with CCL25; anti-CCL25 antibody neutralization American journal of physiology. Gastrointestinal and liver physiology High 14592943
2004 CCL25 is aberrantly expressed on hepatic endothelium in primary sclerosing cholangitis (PSC) and activates α4β7 binding to MAdCAM-1 on hepatic endothelium, thereby recruiting gut-primed CCR9+ T cells to the liver and mediating extra-intestinal inflammation. Immunohistochemistry; flow cytometry; in vitro adhesion assay under flow conditions The Journal of experimental medicine High 15557349
2004 CCR9/CCL25 signaling promotes induction and function of CD103 on CD8+ intestinal IEL: CCR9-deficient CD8+ T cells show delayed CD103 induction after entry into small intestinal epithelium; CCL25 induces transient, dose-dependent, pertussis toxin-sensitive CD103-mediated adhesion of CD8+ IEL to E-cadherin. CCR9−/− mice; adoptive transfer; pertussis toxin treatment; adhesion assay to mEFc fusion protein European journal of immunology High 15368288
2006 CCL25 expression in small intestinal epithelial cells is regulated by caudal-related homeobox (Cdx) transcription factors: Cdx proteins bind to putative Cdx sites in the CCL25 promoter (EMSA), and co-transfection of Cdx-1 or Cdx-2 significantly increases CCL25 promoter activity and endogenous CCL25 mRNA in intestinal cell lines. Promoter deletion analysis; EMSA; co-transfection/reporter assay; RT-PCR Journal of immunology High 16517733
2006 CCL25 and CCL28 redundantly recruit IgA+ plasmablasts to the small intestinal lamina propria after rotavirus infection; combined antibody blockade of both chemokines (but neither alone) prevents IgA+ plasmablast accumulation; CCR9 and α4β7 are coexpressed on IgA+ plasmablasts and both pathways are required. CCR9 knockout mice; in vivo antibody neutralization (anti-CCL25, anti-CCL28, anti-α4); flow cytometry Journal of immunology High 16670280
2007 CCL25 is required for antigen-dependent accumulation of CCR9high memory-phenotype CD8+ T cells within the small intestinal lamina propria and epithelium, but is dispensable for generating CCR9high memory phenotype in mesenteric lymph nodes. CCL25−/− mice; TCR-transgenic naive CD8+ T cell transfer; oral antigen sensitization; flow cytometry Journal of immunology High 17548595
2007 CCL25-stimulated α4β1-integrin-mediated adhesion of thymocytes to CS-1/fibronectin and VCAM-1 requires activation of Rac and Rap1 GTPases; downstream effectors WAVE2 and RAPL (but not RIAM) are required for efficient CCL25-triggered integrin-dependent adhesion; Rac-WAVE2 drives post-adhesion actin-dependent spreading. GTPase activity assays; shRNA knockdown of WAVE2, RAPL, RIAM; adhesion assays on CS-1/FN and VCAM-1; Molt-4 CCR9+/α4β1+ cell line Journal of leukocyte biology High 17510295
2008 CCL25 and CCL28 both trigger α4β7-dependent lymphocyte arrest on immobilized MAdCAM-1 under shear flow conditions, but have no effect on α4β1/VCAM-1-mediated adhesion, demonstrating selective activation of α4β7 integrin. Flow-based adhesion assay with immobilized chemokines on MAdCAM-1 and VCAM-1; integrin-blocking antibodies American journal of physiology. Gastrointestinal and liver physiology High 18308860
2008 Androgen withdrawal increases thymic epithelial cell (TEC) production of CCL25, particularly by UEA+ TEC; blockade of CCL25 abrogates the effects of castration by impairing early thymic progenitor (ETP) entry, retarding thymocyte development, and limiting thymic size increase. Castration model; CCL25 antibody blockade; adoptive transfer of quantified precursors; flow cytometry of ETP and TEC populations Blood High 18694999
2008 CCR9-CCL25 interactions promote migration and invasion of cutaneous melanoma cells expressing CCR9 toward CCL25 gradients in a CCR9-dependent manner (blocked by anti-CCR9 antibody or CCR9 siRNA); CCR9+ melanoma cells also express α4β1 integrin, suggesting cooperative adhesion mechanisms. In vitro migration and invasion assays; anti-CCR9 antibody and siRNA knockdown; flow cytometry; RT-PCR Clinical cancer research High 18245522
2009 P-selectin and CCL25 are periodically co-expressed in the thymus and both are essential components of the thymic gate-keeping mechanism for T-cell progenitor (TCP) importation; sphingosine-1-phosphate (S1P) from peripheral lymphocytes feeds back to regulate thymic P-selectin expression and TCP receptivity. Periodic expression analysis; P-selectin ligand mutant mice; competitive TCP reconstitution; S1P manipulation The Journal of experimental medicine High 19289576
2009 Ezrin is a key molecule in CCL25-induced MOLT4 cell polarization and invasive behavior: CCL25 induces pseudopodium formation and ERM translocation from cytoplasm to cell membrane; ezrin silencing by miRNA impairs CCL25-induced cell polarization and invasion. miRNA-mediated ezrin silencing; confocal microscopy of ERM translocation; invasion assay Leukemia research Medium 20036004
2010 CCR9-CCL25 signaling activates PI3K/Akt and ERK1/2 pathways in prostate cancer cells to upregulate antiapoptotic proteins (PI3K, AKT, ERK1/2, GSK-3β) and suppress caspase-3 activation; PI3K inhibitor wortmannin abrogates these effects; in vivo tumor burden is reduced by CCL25 neutralizing antibodies combined with etoposide. PI3K inhibitor (wortmannin); anti-CCR9 monoclonal antibodies; caspase-3 assay; in vivo mouse xenograft International journal of cancer Medium 20127861
2010 CCL25 induces RhoA activation and MLC phosphorylation (RhoA-ROCK-MLC axis) in MOLT4 cells; C3 exoenzyme and ROCK inhibitor Y-27632 block CCL25-induced cell migration and chemotaxis. GTPase activity assay; pharmacological inhibitors (C3 exoenzyme, Y-27632); migration and chemotaxis assay Leukemia research Medium 20855113
2010 CCL25 stimulates migration of human subchondral mesenchymal progenitor cells in a CCR9-dependent fashion, as demonstrated by chemotaxis assay; these progenitors express CCR9 mRNA and protein. 96-well chemotaxis assay; gene expression analysis (real-time PCR); immunohistochemistry for CCR9 Osteoarthritis and cartilage Medium 20709179
2011 CCL25 promotes breast cancer cell (MDA-MB-231) migration and invasion through CCR9; neutralizing CCR9-CCL25 interactions impairs migration and invasion; CCL25 enhances expression of active MMP-1, -9, -11, and -13 in a CCR9-dependent fashion. Migration and invasion assays; anti-CCR9 neutralization; ELISA for active MMP proteins International journal of oncology Medium 21344163
2011 CCL25/CCR9 interactions regulate colitis in the large intestine: CCR9−/− mice are more susceptible to DSS colitis, with accumulation of activated macrophages, elevated Th1/Th17 cytokines, and altered DC subset balance in mesenteric lymph nodes during recovery. CCR9−/− mice; DSS colitis model; flow cytometry; cytokine quantification (mRNA and protein); IBD scoring PloS one High 21283540
2012 Multiple myeloma cells produce CCL25 as a major chemoattractant for bone marrow mesenchymal stromal cells (MSCs); CCL25-recruited MSCs favor myeloma cell proliferation and protect against apoptosis by enhancing AKT and ERK activity and upregulating CyclinD2, CDK4, and Bcl-XL. In vitro and in vivo migration assays; CCL25 neutralization; co-culture proliferation/apoptosis assays; western blotting; intrafemoral coengraftment Stem cells High 22102554
2013 CCL25-induced drug resistance in T-ALL MOLT4 cells involves phosphorylated ERM (p-ERM) serving as a scaffold linking P-glycoprotein (P-gp) to F-actin; ERM silencing by shRNA releases P-gp from F-actin and restores drug sensitivity. shRNA-mediated ERM knockdown; co-immunoprecipitation of p-ERM, P-gp, and F-actin; P-gp functional assay PloS one High 23326330
2014 CCL25-stimulated endometrial stromal cell-derived Treg differentiation is mediated via AKT/STAT3 signaling; ESC/macrophage-derived TECK induces Treg differentiation, increases IL-10, TGF-β, and CD73 expression, and represses Treg apoptosis (reducing Fas/FasL); anti-TECK neutralizing antibodies inhibit these effects. Co-culture experiments; AKT/STAT3 signaling analysis; anti-TECK neutralizing antibodies; in vitro and in vivo trials Cell death & disease Medium 25275597
2017 CCL25 induces Wnt5a expression in MOLT4 T-ALL cells via promotion of PKC expression and activation; Wnt5a then promotes cell migration, invasion, actin polarization, and lamellipodia/filopodia formation via PI3K/Akt-RhoA pathway; PI3K/Akt or RhoA knockdown/inhibition rescues these effects. Transwell invasion/migration assays; western blotting; siRNA and inhibitor knockdown of PI3K/Akt and RhoA; confocal and scanning electron microscopy; mouse xenograft Oncotarget Medium 28380463
2020 CCL25 acts via the Gαi-coupled receptor CCR9 to inhibit glucose-induced insulin secretion in a concentration-dependent manner, enhance cytokine-induced apoptosis, and reduce cAMP levels in human and mouse islets; these effects are blocked by the CCR9 antagonist vercirnon. Insulin secretion assay; cAMP accumulation assay; apoptosis assay in primary human and mouse islets; CCR9 antagonist (vercirnon) Metabolism: clinical and experimental High 33058852
2021 CCL25 stimulates RA FLS and monocyte migration via p38 and ERK phosphorylation; CCL25 polarizes RA monocytes into non-traditional M1 macrophages producing IL-8 and CCL2 via p38 and ERK cascades; CCL25-induced osteoclastogenesis is regulated by RANK, cathepsin K, and TNF-α but not RANKL. p38 and ERK inhibitors; flow cytometry; cytokine ELISA; osteoclast differentiation assay in RA synovial tissue/cells European journal of immunology Medium 33347617
2022 CCL25 promotes increased endothelial permeability by reducing tight junction protein expression via activation of the P38 MAPK pathway; NF-κB inhibition in HPMECs decreases CCL25 expression; recombinant CCL25 increases cell permeability and inflammatory cytokine expression. LPS-stimulated HPMECs; TEER measurement; FITC-fluorescence intensity; luciferase assays; chromatin immunoprecipitation; P38 MAPK pathway analysis Infection and drug resistance Medium 35782530

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2000 Lymphocyte CC chemokine receptor 9 and epithelial thymus-expressed chemokine (TECK) expression distinguish the small intestinal immune compartment: Epithelial expression of tissue-specific chemokines as an organizing principle in regional immunity. The Journal of experimental medicine 493 10974041
2000 The chemokine TECK is expressed by thymic and intestinal epithelial cells and attracts double- and single-positive thymocytes expressing the TECK receptor CCR9. European journal of immunology 292 10602049
2002 CCL25 mediates the localization of recently activated CD8alphabeta(+) lymphocytes to the small-intestinal mucosa. The Journal of clinical investigation 273 12393847
2004 Hepatic endothelial CCL25 mediates the recruitment of CCR9+ gut-homing lymphocytes to the liver in primary sclerosing cholangitis. The Journal of experimental medicine 251 15557349
1997 TECK: a novel CC chemokine specifically expressed by thymic dendritic cells and potentially involved in T cell development. Immunity 225 9285413
2002 The intestinal chemokine thymus-expressed chemokine (CCL25) attracts IgA antibody-secreting cells. The Journal of experimental medicine 159 11805153
2000 Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK. Journal of immunology (Baltimore, Md. : 1950) 154 10706668
1999 Cutting edge: identification of the orphan chemokine receptor GPR-9-6 as CCR9, the receptor for the chemokine TECK. Journal of immunology (Baltimore, Md. : 1950) 147 10229797
2011 CCL25/CCR9 interactions regulate large intestinal inflammation in a murine model of acute colitis. PloS one 120 21283540
2008 Activation of CCR9/CCL25 in cutaneous melanoma mediates preferential metastasis to the small intestine. Clinical cancer research : an official journal of the American Association for Cancer Research 118 18245522
2006 Antibody blockade of CCL25/CCR9 ameliorates early but not late chronic murine ileitis. Gastroenterology 114 17101325
2010 Chemokine profile of synovial fluid from normal, osteoarthritis and rheumatoid arthritis patients: CCL25, CXCL10 and XCL1 recruit human subchondral mesenchymal progenitor cells. Osteoarthritis and cartilage 95 20709179
2012 Bone marrow-derived mesenchymal stromal cells are attracted by multiple myeloma cell-produced chemokine CCL25 and favor myeloma cell growth in vitro and in vivo. Stem cells (Dayton, Ohio) 87 22102554
2002 Characterization of CCR9 expression and CCL25/thymus-expressed chemokine responsiveness during T cell development: CD3(high)CD69+ thymocytes and gammadeltaTCR+ thymocytes preferentially respond to CCL25. Journal of immunology (Baltimore, Md. : 1950) 87 11751956
2009 Thymic progenitor homing and lymphocyte homeostasis are linked via S1P-controlled expression of thymic P-selectin/CCL25. The Journal of experimental medicine 85 19289576
2014 CD4+Foxp3+ regulatory T cell differentiation mediated by endometrial stromal cell-derived TECK promotes the growth and invasion of endometriotic lesions. Cell death & disease 84 25275597
2016 Intestinal CCL25 expression is increased in colitis and correlates with inflammatory activity. Journal of autoimmunity 82 26873648
2006 Redundant role of chemokines CCL25/TECK and CCL28/MEC in IgA+ plasmablast recruitment to the intestinal lamina propria after rotavirus infection. Journal of immunology (Baltimore, Md. : 1950) 81 16670280
2007 Impaired accumulation of antigen-specific CD8 lymphocytes in chemokine CCL25-deficient intestinal epithelium and lamina propria. Journal of immunology (Baltimore, Md. : 1950) 80 17548595
2004 CCL25/CCR9 promotes the induction and function of CD103 on intestinal intraepithelial lymphocytes. European journal of immunology 80 15368288
2002 Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR. European journal of immunology 80 11981810
2021 The Roles of CCR9/CCL25 in Inflammation and Inflammation-Associated Diseases. Frontiers in cell and developmental biology 78 34490243
2008 Role of beta7 integrin and the chemokine/chemokine receptor pair CCL25/CCR9 in modeled TNF-dependent Crohn's disease. Gastroenterology 76 18439426
2020 Intratumoral delivery of CCL25 enhances immunotherapy against triple-negative breast cancer by recruiting CCR9+ T cells. Science advances 74 32064335
2011 CCL25 mediates migration, invasion and matrix metalloproteinase expression by breast cancer cells in a CCR9-dependent fashion. International journal of oncology 74 21344163
2003 Demonstration of functional role of TECK/CCL25 in T lymphocyte-endothelium interaction in inflamed and uninflamed intestinal mucosa. American journal of physiology. Gastrointestinal and liver physiology 70 14592943
1999 TECK, an efficacious chemoattractant for human thymocytes, uses GPR-9-6/CCR9 as a specific receptor. Blood 66 10498628
2008 Human periosteum-derived progenitor cells express distinct chemokine receptors and migrate upon stimulation with CCL2, CCL25, CXCL8, CXCL12, and CXCL13. European journal of cell biology 65 18501472
2013 Recombinant TNFα as oral vaccine adjuvant protects European sea bass against vibriosis: insights into the role of the CCL25/CCR9 axis. Fish & shellfish immunology 64 23932985
2008 CCL25 increases thymopoiesis after androgen withdrawal. Blood 62 18694999
2008 CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. American journal of physiology. Gastrointestinal and liver physiology 60 18308860
2006 Expression of Dll4 and CCL25 in Foxn1-negative epithelial cells in the post-natal thymus. International immunology 59 17158094
2007 Commensal bacteria and expression of two major intestinal chemokines, TECK/CCL25 and MEC/CCL28, and their receptors. PloS one 56 17653288
2017 Increased CCL25 and T Helper Cells Expressing CCR9 in the Salivary Glands of Patients With Primary Sjögren's Syndrome: Potential New Axis in Lymphoid Neogenesis. Arthritis & rheumatology (Hoboken, N.J.) 52 28622456
2001 Blocking of c-FLIP(L)--independent cycloheximide-induced apoptosis or Fas-mediated apoptosis by the CC chemokine receptor 9/TECK interaction. Blood 52 11493434
2006 Functional characterization of the CCL25 promoter in small intestinal epithelial cells suggests a regulatory role for caudal-related homeobox (Cdx) transcription factors. Journal of immunology (Baltimore, Md. : 1950) 50 16517733
2013 Activated ERM protein plays a critical role in drug resistance of MOLT4 cells induced by CCL25. PloS one 47 23326330
2011 CCR9-CCL25 interactions promote cisplatin resistance in breast cancer cell through Akt activation in a PI3K-dependent and FAK-independent fashion. World journal of surgical oncology 47 21539750
2010 CCR9 mediates PI3K/AKT-dependent antiapoptotic signals in prostate cancer cells and inhibition of CCR9-CCL25 interaction enhances the cytotoxic effects of etoposide. International journal of cancer 47 20127861
2010 CCL25-CCR9 interaction modulates ovarian cancer cell migration, metalloproteinase expression, and invasion. World journal of surgical oncology 47 20649989
2010 Monocytes/macrophages express chemokine receptor CCR9 in rheumatoid arthritis and CCL25 stimulates their differentiation. Arthritis research & therapy 46 20738854
2006 Role of CCL25/CCR9 in immune homeostasis and disease. Expert review of clinical immunology 46 20477631
2000 CCR9A and CCR9B: two receptors for the chemokine CCL25/TECK/Ck beta-15 that differ in their sensitivities to ligand. Journal of immunology (Baltimore, Md. : 1950) 45 10640743
2020 CCR9 and CCL25: A review of their roles in tumor promotion. Journal of cellular physiology 44 32401349
2002 Involvement of CCL25 (TECK) in the generation of the murine small-intestinal CD8alpha alpha+CD3+ intraepithelial lymphocyte compartment. European journal of immunology 44 12442331
2015 CCR9-CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway. Medical oncology (Northwood, London, England) 42 25691296
2014 CCR9/CCL25 expression in non-small cell lung cancer correlates with aggressive disease and mediates key steps of metastasis. Oncotarget 42 25296976
2008 Human IgA-secreting cells induced by intestinal, but not systemic, immunization respond to CCL25 (TECK) and CCL28 (MEC). European journal of immunology 42 19003934
2002 Pivotal role of CCL25 (TECK)-CCR9 in the formation of gut cryptopatches and consequent appearance of intestinal intraepithelial T lymphocytes. International immunology 42 12096027
2006 Expression of TECK/CCL25 and MEC/CCL28 chemokines and their respective receptors CCR9 and CCR10 in porcine mucosal tissues. Veterinary immunology and immunopathology 40 16839611
2011 Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer. International journal of oncology 39 21637913
2010 Angiotensin-converting enzyme inhibition down-regulates the pro-atherogenic chemokine receptor 9 (CCR9)-chemokine ligand 25 (CCL25) axis. The Journal of biological chemistry 39 20504763
2016 CCL25/CCR9 Signal Promotes Migration and Invasion in Hepatocellular and Breast Cancer Cell Lines. DNA and cell biology 36 27008282
2017 Wnt5a and CCL25 promote adult T-cell acute lymphoblastic leukemia cell migration, invasion and metastasis. Oncotarget 33 28380463
2002 Role of the CC chemokine receptor 9/TECK interaction in apoptosis. Apoptosis : an international journal on programmed cell death 31 11997671
2018 CD33+ CD14+ CD11b+ HLA-DR- monocytic myeloid-derived suppressor cells recruited and activated by CCR9/CCL25 are crucial for the pathogenic progression of endometriosis. American journal of reproductive immunology (New York, N.Y. : 1989) 30 30375700
2016 Rainbow trout CK9, a CCL25-like ancient chemokine that attracts and regulates B cells and macrophages, the main antigen presenting cells in fish. Oncotarget 29 27003360
2012 CCL25 induces α₄β₇ integrin-dependent migration of IL-17⁺ γδ T lymphocytes during an allergic reaction. European journal of immunology 29 22539297
2012 Cloning, expression and characterization of CCL21 and CCL25 chemokines in zebrafish. Developmental and comparative immunology 29 22842207
2012 Generation of antigen-specific immunity following systemic immunization with DNA vaccine encoding CCL25 chemokine immunoadjuvant. Human vaccines & immunotherapeutics 29 23151454
2010 Abnormal regulation of chemokine TECK and its receptor CCR9 in the endometriotic milieu is involved in pathogenesis of endometriosis by way of enhancing invasiveness of endometrial stromal cells. Cellular & molecular immunology 27 20081876
2009 Ezrin is a key molecule in the metastasis of MOLT4 cells induced by CCL25/CCR9. Leukemia research 27 20036004
2007 Intracellular signaling required for CCL25-stimulated T cell adhesion mediated by the integrin alpha4beta1. Journal of leukocyte biology 27 17510295
2013 Mesenchymal stem cells and their chondrogenic differentiated and dedifferentiated progeny express chemokine receptor CCR9 and chemotactically migrate toward CCL25 or serum. Stem cell research & therapy 26 23958031
2007 Expression of mucosal chemokines TECK/CCL25 and MEC/CCL28 during fetal development of the ovine mucosal immune system. Immunology 23 17250588
2019 A Subset of CCL25-Induced Gut-Homing T Cells Affects Intestinal Immunity to Infection and Cancer. Frontiers in immunology 22 30863398
2019 Toll-Like Receptor 4 Promotes Th17 Lymphocyte Infiltration Via CCL25/CCR9 in Pathogenesis of Experimental Autoimmune Encephalomyelitis. Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology 22 31065973
2021 CCL25 and CCR9 is a unique pathway that potentiates pannus formation by remodeling RA macrophages into mature osteoclasts. European journal of immunology 21 33347617
2005 Transient expression of CC chemokine TECK in the ovary during ovulation: its potential role in ovulation. American journal of reproductive immunology (New York, N.Y. : 1989) 21 15833102
2020 Parenterally Administered Porcine Epidemic Diarrhea Virus-Like Particle-Based Vaccine Formulated with CCL25/28 Chemokines Induces Systemic and Mucosal Immune Protectivity in Pigs. Viruses 20 33023277
2019 Decreased circulating CXCR3 + CCR9+T helper cells are associated with elevated levels of their ligands CXCL10 and CCL25 in the salivary gland of patients with Sjögren's syndrome to facilitate their concerted migration. Scandinavian journal of immunology 20 31733111
2014 CCL25/CCR9 interactions are not essential for colitis development but are required for innate immune cell protection from chronic experimental murine colitis. Inflammatory bowel diseases 19 24874458
2020 A CCL25 chemokine functions as a chemoattractant and an immunomodulator in black rockfish, Sebastes schlegelii. Fish & shellfish immunology 18 32135342
2020 CCL25 promotes the migration and invasion of non-small cell lung cancer cells by regulating VEGF and MMPs in a CCR9-dependent manner. Experimental and therapeutic medicine 18 32346420
2020 The role of the CCL25-CCR9 axis in beta-cell function: potential for therapeutic intervention in type 2 diabetes. Metabolism: clinical and experimental 18 33058852
2010 Role of Rho-ROCK signaling in MOLT4 cells metastasis induced by CCL25. Leukemia research 16 20855113
2021 LINC00853 restrains T cell acute lymphoblastic leukemia invasion and infiltration by regulating CCR9/CCL25. Molecular immunology 15 34808497
2018 Chemokine CCL25 Induces Migration and Extracellular Matrix Production of Anulus Fibrosus-Derived Cells. International journal of molecular sciences 14 30060561
2014 CCL25/CCR9 interactions regulate the function of iNKT cells in oxazolone-induced colitis in mice. PloS one 14 24936795
2022 CCL25 Inhibition Alleviates Sepsis-Induced Acute Lung Injury and Inflammation. Infection and drug resistance 13 35782530
2020 Impaired CCR9/CCL25 signalling induced by inefficient dendritic cells contributes to intestinal immune imbalance in nonalcoholic steatohepatitis. Biochemical and biophysical research communications 13 33310185
2013 Anti-CCL25 antibody prolongs skin allograft survival by blocking CCR9 expression and impairing splenic T-cell function. Archivum immunologiae et therapiae experimentalis 12 23456208
2008 Association between decreased CXCL12 and CCL25 expression and increased apoptosis in lymphoid tissues of cynomolgus macaques during SIV infection. Journal of medical primatology 12 19187430
2023 PCSK9 promotes tumor cell proliferation and migration by facilitating CCL25 secretion in esophageal squamous cell carcinoma. Oncology letters 11 37854863
2022 ZIM3 activation of CCL25 expression in pulmonary metastatic nodules of osteosarcoma recruits M2 macrophages to promote metastatic growth. Cancer immunology, immunotherapy : CII 11 36161509
2010 Partial characterization and distribution of the chemokines CCL25 and CCL28 in the bovine system. Veterinary immunology and immunopathology 11 20688401
2018 Delayed release of chemokine CCL25 with bioresorbable microparticles for mobilization of human mesenchymal stem cells. Acta biomaterialia 10 29408710
2018 Dose-Dependent Effect of Mesenchymal Stromal Cell Recruiting Chemokine CCL25 on Porcine Tissue-Engineered Healthy and Osteoarthritic Cartilage. International journal of molecular sciences 10 30583576
2017 Molecular cloning and expression analysis of CCL25 and its receptor CCR9s from Epinephelus coioides post Cryptocaryon irritans infection. Fish & shellfish immunology 10 28624470
2021 Therapies with CCL25 require controlled release via microparticles to avoid strong inflammatory reactions. Journal of nanobiotechnology 8 33766057
2019 CCL25-Supplemented Hyaluronic Acid Attenuates Cartilage Degeneration in a Guinea Pig Model of Knee Osteoarthritis. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 8 30977553
2024 Piezo1 activation on microglial cells exacerbates demyelination in sepsis by influencing the CCL25/GRP78 pathway. International immunopharmacology 7 39236454
2023 CCR9-CCL25 mediated plasmacytoid dendritic cell homing and contributed the immunosuppressive microenvironment in gastric cancer. Translational oncology 7 37126939
2008 Decreased expression of intestinal chemokine TECK/CCL25 in experimental obstructive jaundice and its reversal following internal biliary drainage. Journal of gastroenterology 7 18592157
2022 Antigen-Presenting Cells and T Cells Interact in a Specific Area of the Intestinal Mucosa Defined by the Ccl25-Ccr9 Axis in Medaka. Frontiers in immunology 6 35185906
2022 CCL25/CCR9 interaction promotes the malignant behavior of salivary adenoid cystic carcinoma via the PI3K/AKT signaling pathway. PeerJ 6 36003306
2021 CCL25 Signaling in the Tumor Microenvironment. Advances in experimental medicine and biology 6 34286444
2018 CCL25 chemokine-guided stem cell attraction: an assessment of possible benefits and risks. Regenerative medicine 6 30284497
2021 Dissecting the contribution of single nucleotide polymorphisms in CCR9 and CCL25 genomic regions to the celiac disease phenotype. Journal of translational autoimmunity 5 34901814
2008 Importance of CCL25 in the attraction of T cells and the role of IL-7 on the signaling pathways in intestinal epithelial cells. Immunobiology 5 19249122