Affinage

CCL19

C-C motif chemokine 19 · UniProt Q99731

Length
98 aa
Mass
11.0 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL19 is a homeostatic CC chemokine that directs lymphocyte and dendritic cell trafficking to secondary lymphoid organs by signaling through its primary receptor CCR7. CCL19 binds CCR7 to induce calcium mobilization, PI3K/Akt, ERK, and NF-κB signaling, and uniquely triggers arrestin 3-dependent CCR7 internalization and desensitization—unlike its co-ligand CCL21—enabling DCs to act as both gradient sensors and chemokine sinks for self-organized collective migration (PMID:9701028, PMID:18802075, PMID:37656776). Atypical receptors ACKR4 and CCRL2 scavenge CCL19 without canonical signaling, shaping tissue chemokine gradients critical for dendritic cell egress and immune homeostasis (PMID:16791897, PMID:26976955). Beyond lymphoid trafficking, CCL19/CCR7 signaling couples lymph node entry to S1P1-dependent egress via ERK5/KLF-2, promotes T cell activation-induced cell death through Fas ligand upregulation, drives TH2 differentiation via STAT5 phosphorylation, facilitates HIV-1 integration in resting CD4+ T cells through NF-κB, and orchestrates tertiary lymphoid structure formation in tumors (PMID:22334704, PMID:16973962, PMID:37956733, PMID:27459960, PMID:39137726).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1998 High

    Identification of CCL19 as a high-affinity CCR7 ligand that selectively chemoattracts T and B cells established the molecular basis of lymphocyte guidance to lymph node parafollicular zones.

    Evidence Ligand binding assay, calcium mobilization, chemotaxis, ISH in human lymphoid tissues

    PMID:9701028

    Open questions at the time
    • CCL19 vs CCL21 functional divergence at CCR7 not yet dissected
    • in vivo requirement for CCL19 in lymph node homing not tested
  2. 2000 High

    Co-deletion of CCL19 and CCL21 in plt/plt mice disrupted T cell and DC trafficking to lymphoid organs, proving that CCR7 ligands are non-redundant with other chemokines for lymphoid organogenesis, while identification of CCX-CKR (ACKR4) as a second CCL19-binding receptor revealed a scavenging axis distinct from CCR7.

    Evidence plt/plt genetic model with bone marrow reconstitution and ISH; radioligand binding and competition panel for CCX-CKR

    PMID:10706668 PMID:11070085

    Open questions at the time
    • Individual contributions of CCL19 vs CCL21 unresolved in plt/plt model
    • ACKR4 scavenging mechanism and biological role in vivo unknown
  3. 2001 High

    Demonstration that CCL19 is transcytosed across HEVs to mediate T cell arrest, and that CCL19 uniquely induces CCR7 internalization and desensitization unlike CCL21, revealed two mechanisms—luminal presentation and biased receptor regulation—by which CCL19 controls lymphocyte entry.

    Evidence Footpad injection with plt/plt rescue; flow cytometry internalization and re-expression assays in T cells

    PMID:11342595 PMID:11745346

    Open questions at the time
    • Molecular basis of differential CCR7 internalization by CCL19 vs CCL21 unknown
    • transcytosis receptor/pathway not identified
  4. 2003 High

    Mapping of CCL19-triggered DC signaling to PGE2-dependent PI3K/Akt activation and calcium flux defined the intracellular requirements for chemotaxis, with PLC and calcium being essential while PI3K was dispensable for migration per se.

    Evidence Pharmacological pathway dissection in human monocyte-derived DCs with migration and calcium readouts

    PMID:14592837

    Open questions at the time
    • Relative contributions of parallel signaling arms to directional sensing vs speed not resolved
    • role of Rho GTPases not addressed
  5. 2006 High

    Three discoveries converged to define CCL19's broader biological actions beyond migration: ACKR4 was shown to constitutively scavenge and degrade CCL19 via a beta-arrestin-independent caveolar pathway; CCL19/CCL21 were found to promote T cell AICD via Fas ligand upregulation; and an N-terminal truncation antagonist (CCL19(8-83)) specifically blocked CCL19 signaling in vivo, enabling dissection of CCL19 vs CCL21 roles in immune priming.

    Evidence HEK293 internalization/degradation assays with siRNA; plt/plt OVA immunization with AICD readout; specific antagonist in allogeneic CTL assay

    PMID:15231820 PMID:16791897 PMID:16973962

    Open questions at the time
    • In vivo gradient-shaping role of ACKR4 scavenging not demonstrated
    • AICD mechanism beyond Fas ligand not explored
    • antagonist selectivity in complex immune responses not fully tested
  6. 2008 High

    Arrestin 3 was identified as the specific mediator of CCL19-induced CCR7 internalization and migration, resolving why CCL19 and CCL21 produce divergent receptor fates despite sharing CCR7.

    Evidence siRNA knockdown and arrestin double-KO MEF reconstitution with GFP-tagged arrestins, migration assays

    PMID:18802075

    Open questions at the time
    • Downstream signaling events from arrestin 3-CCR7 complexes not characterized
    • phosphorylation code on CCR7 C-terminus not mapped
  7. 2010 High

    CCL19-deficient mice with intact CCL21 showed normal DC migration and T cell priming, establishing that CCL19 is dispensable for constitutive DC homeostasis and revealing functional redundancy within the CCR7 ligand pair for steady-state trafficking.

    Evidence CCL19-KO mice with flow cytometry of DC localization and T cell priming assays

    PMID:20201039

    Open questions at the time
    • Non-redundant roles of CCL19 in inflammation or specific immune contexts not yet identified
    • whether CCL19 is required for fine-tuning gradient shape in vivo unclear
  8. 2012 High

    CCL19/CCR7 signaling was found to activate ERK5→KLF-2→S1P1 in T cells, coupling CCL19-driven lymph node entry to subsequent S1P1-dependent egress—an unexpected feedback linking chemokine and sphingolipid receptor pathways.

    Evidence CCL19 stimulation of T cells, ERK5 conditional KO (ERK5flox/flox/Lck-Cre), S1P migration assay

    PMID:22334704

    Open questions at the time
    • Whether CCL21 induces the same ERK5-KLF2-S1P1 cascade not tested
    • in vivo egress kinetics in CCL19-only vs CCL21-only settings unknown
  9. 2015 High

    NMR solution structure of CCL19 revealed overlapping binding sites for CCR7 and PSGL-1 N-termini, providing a structural basis for co-receptor enhancement of CCL19-driven T cell recruitment.

    Evidence NMR structure determination with chemical shift perturbation mapping

    PMID:26115234

    Open questions at the time
    • No ternary complex structure of CCL19-CCR7-PSGL-1 available
    • functional validation of competitive binding in cell-based assays not shown
  10. 2016 High

    Genetic epistasis showed ACKR4 scavenging of CCL19 in skin is required for DC egress to lymph nodes—Ackr4 loss impairs Langerhans cell migration, fully rescued by CCL19 deletion—while CCL19 was shown to facilitate HIV-1 integration in resting CD4+ T cells through NF-κB-dependent integrase stabilization.

    Evidence Ackr4/Ccl19 double-KO mice with DC tracking; NF-κB-mutant HIV, pathway inhibitors, co-IP of integrase with Pin1

    PMID:26976955 PMID:27459960

    Open questions at the time
    • Whether ACKR4-CCL19 axis operates similarly in mucosal tissues unknown
    • HIV integration mechanism confirmed only in vitro
    • Pin1-integrase interaction specificity to CCL19 context not verified
  11. 2019 High

    CCL19 produced by reactive astrocytes was shown to retain CCR7+ lymphoma cells in brain parenchyma, establishing a non-immune stromal source of CCL19 as critical for CNS lymphoma pathogenesis.

    Evidence CCL19-deleted mice and CCR7-deleted lymphoma cells with two-photon microscopy and xenograft models

    PMID:31526758

    Open questions at the time
    • Whether this mechanism applies to other brain-tropic malignancies unknown
    • astrocyte signals inducing CCL19 not identified
  12. 2023 High

    Two parallel advances redefined CCL19's roles: CCR7 was shown to function as both sensor and sink for CCL19, with ligand consumption enabling self-generated gradients for collective DC migration; separately, CCL19 was found to promote TH2 differentiation via STAT5 phosphorylation, with Ccl19-KO mice showing attenuated allergic airway disease.

    Evidence Live-cell DC imaging with computational modeling; Ccl19-KO in OVA asthma model with STAT5 flow cytometry and RNA-seq

    PMID:37656776 PMID:37956733

    Open questions at the time
    • Physical basis of CCR7 ligand consumption kinetics not resolved at structural level
    • whether STAT5 activation is direct or mediated via IL-2 autocrine loop unclear
  13. 2024 High

    CCL19-secreting fibroblasts were identified as organizers of tertiary lymphoid structures in colorectal cancer liver metastasis, with exogenous CCL19 promoting TLS neogenesis and anti-tumor immunity in vivo.

    Evidence Single-cell RNA-seq, spatial transcriptomics, humanized mouse model with CCL19 treatment

    PMID:39137726

    Open questions at the time
    • Molecular signals initiating CCL19 expression in tumor fibroblasts not defined
    • whether CCL19 alone is sufficient or acts with CCL21 for TLS maturation unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis of differential arrestin recruitment by CCL19 vs CCL21 at CCR7, the phosphorylation barcode on CCR7 that distinguishes the two ligands, whether CCL19's STAT5-mediated TH2-polarizing function operates independently of its chemotactic role, and how CCL19 production is transcriptionally regulated in non-immune stromal cells such as astrocytes and fibroblasts.
  • No CCR7 phosphosite-resolved structure with CCL19 vs CCL21
  • STAT5 activation mechanism (direct vs indirect) unresolved
  • transcriptional regulation of CCL19 in stromal cells poorly characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 3
Partners
ACKR4ARRB2CCR7CCRL2PSGL1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 CCL19 (ELC) and CCL21 (SLC) are co-expressed by T zone stromal cells in secondary lymphoid organs; deletion of both ELC and SLC genes occurs in plt/plt mice, which show disrupted T cell and dendritic cell trafficking to lymphoid tissues. Bone marrow reconstitution, double in situ hybridization, genetic mouse model (plt/plt) Proceedings of the National Academy of Sciences of the United States of America High 11070085
2001 CCL19 is transcytosed from perivascular spaces to the luminal surface of high endothelial venules (HEVs), enabling CCR7-mediated T cell arrest and lymph node homing. In situ hybridization, immunostaining, footpad injection of CCL19 in mice, T cell trafficking assay in plt/plt mice The Journal of experimental medicine High 11342595
2000 MRP1-mediated transport of leukotriene C4 (LTC4) is required for optimal dendritic cell chemotaxis toward CCL19; cysteinyl leukotrienes promote CCL19-dependent DC migration from the epidermis to lymph nodes. MRP1 knockout mice, exogenous LTC4/LTD4 rescue, in vitro chemotaxis assay, in vivo CCL19 antagonism Cell High 11114332
2001 CCL19 induces rapid, concentration-dependent internalization of its receptor CCR7 and receptor desensitization, whereas CCL21 does not internalize CCR7; internalized CCR7 is re-expressed after CCL19 removal. Flow cytometry, receptor internalization assays, functional re-stimulation assays in T lymphocytes and CCR7-bearing cells European journal of immunology High 11745346
2008 CCR7 internalization following CCL19 (but not CCL21) binding requires arrestin 3 (beta-arrestin 2); siRNA knockdown of arrestin 3 abolishes CCL19-induced CCR7 internalization and blocks migration to CCL19 but not CCL21. siRNA knockdown of arrestin 2/3 in HuT 78 cells, arrestin 2−/−/arrestin 3−/− MEF reconstitution with GFP-tagged arrestins, immunofluorescence microscopy, migration assay Journal of immunology High 18802075
2000 CCL19 (ELC) binds with high affinity to a novel atypical receptor, CCX-CKR (provisionally CCR10), in addition to CCR7; this receptor also binds CCL21 and CCL25 (TECK) but not most other chemokines. Stalkokine adhesion assay, radiolabeled ligand binding, competition with >80 chemokines Journal of immunology High 10706668
2006 CCX-CKR (ACKR4) mediates efficient scavenging of CCL19 by internalizing and degrading it; unlike CCR7, CCX-CKR does not become refractory and progressively degrades large quantities of CCL19. CCX-CKR internalization is independent of beta-arrestins and clathrin-coated pits but is blocked by caveolin-1 overexpression. Transfected HEK293 cells, CCL19 internalization and degradation assays, siRNA, caveolin-1 overexpression European journal of immunology High 16791897
2003 CCL19/CCL21-triggered migration of dendritic cells requires prostaglandin E2 (PGE2); PGE2 enables CCR7 coupling to PI3K-mediated phosphorylation of Akt and intracellular calcium mobilization. DC migration to CCL19/CCL21 depends on phospholipase C and calcium flux but not on PI3K. Human monocyte-derived DC cultures, PI3K inhibitors, calcium mobilization assays, migration assays Blood High 14592837
2015 CCL19 solution structure contains a canonical chemokine fold; the N-termini of PSGL-1 and CCR7 have overlapping, competitively binding sites on CCL19, suggesting a mechanism by which PSGL-1 co-receptor expression enhances CCL19-driven T cell recruitment. NMR solution structure determination, chemical shift mapping Biochemistry High 26115234
2009 CCL19 is a specific ligand for the atypical receptor CRAM (CCRL2/CRAM-B); CRAM binds CCL19 with affinity similar to CCR7 but does not trigger calcium mobilization or chemotaxis; instead CRAM constitutively recycles via clathrin-coated pits and internalizes CCL19. Radioactive ligand binding, calcium mobilization assay, migration assay, constitutive recycling assay, anti-CRAM antibody internalization Immunology Medium 20002784
2016 ACKR4 on keratinocytes and dermal lymphatic endothelial cells scavenges dermal CCL19 during cutaneous inflammation; loss of ACKR4 impairs Langerhans cell egress and dermal DC accumulation in lymph nodes, and this defect is fully rescued by genetic deletion of CCL19. Ackr4-deficient mice, Ccl19/Ackr4 double-deficient mice, flow cytometry of skin and draining LN APCs Journal of immunology High 26976955
2010 CCL21 alone is sufficient for DC migration from skin, DC maturation, and efficient T cell priming in vivo; CCL19-deficient mice with intact CCL21 expression show normal DC homeostasis and function, demonstrating CCL19 is redundant for these processes. CCL19-deficient mice with varying CCL21 levels, flow cytometry of DC localization and frequency, T cell priming assays European journal of immunology High 20201039
2011 In a 3D microfluidic system, DCs can sense CCR7 ligand gradients as small as 0.4%; CCL19 and CCL21 show similar sensitivity at small gradients but CCL21 is a more potent directional cue at higher gradients, even when matrix-binding of CCL21 is prevented, suggesting differential receptor signaling rather than matrix binding underlies the difference. Microfluidic 3D gradient device, DC chemotaxis assay in collagen matrices, neutralization of matrix binding Proceedings of the National Academy of Sciences of the United States of America High 21422278
2007 CCL19 (and CCL21) treatment of resting CD4+ T cells increases HIV-1 permissiveness without inducing T cell activation or proliferation, resulting in high levels of integrated HIV-1 DNA and post-integration latency upon restimulation. HIV-1 infection of purified resting CD4+ T cells pre-treated with CCL19/CCL21, integrated HIV DNA quantification, reactivation assay Blood High 17881634
2016 HIV integration in CCL19-treated resting CD4+ T cells requires NF-κB signaling; CCL19 induces phosphorylation of Akt, NF-κB, ERK, and p38, and CCL19 treatment stabilizes HIV integrase by promoting its interaction with Pin1 (reduced by JNK inhibition). HIV mutants lacking NF-κB binding sites in the LTR show 40-fold reduced integration in CCL19-treated cells versus only 5-fold reduction in activated T cells. Pathway inhibitors (PI3K, MEK, JNK, AP-1, NF-κB inhibitors), NF-κB-mutant HIV infection, Alu-LTR and 2-LTR qPCR, co-immunoprecipitation of integrase with Pin1, integration site analysis Retrovirology High 27459960
2012 CCR7/CCL19 signaling in T cells upregulates ERK5 expression and phosphorylation, leading to subsequent induction of KLF-2 and EDG-1 (S1P1), thereby linking CCL19-mediated lymph node entry to S1P1-dependent lymph node egress. CCL19 stimulation of HuT78 and primary murine T cells, Western blot for ERK5/KLF-2/EDG-1, ERK5 conditional KO (ERK5flox/flox/Lck-Cre), migration assay to S1P The Journal of biological chemistry High 22334704
2023 CCR7 functions both as a sensor (directional receptor) and as a sink (ligand consumer) for CCL19 in dendritic cells; CCR7 internalization after CCL19 binding creates a local chemokine gradient, enabling self-organized collective DC migration and long-range guidance. Live-cell imaging of DC chemotaxis, computational modeling, receptor internalization quantification, gradient visualization Science immunology High 37656776
2006 A CCL19 N-terminal truncation mutant CCL19(8-83) specifically antagonizes CCL19-induced chemotaxis and calcium mobilization without affecting CCL21 responses; treatment of mice with this antagonist inhibits cytotoxic T lymphocyte generation against allogeneic dendritic cells, demonstrating a specific role for CCL19 in immune priming. In vitro chemotaxis and calcium mobilization assays, in vivo CCL19 antagonist treatment, allogeneic CTL generation assay The Journal of biological chemistry High 15231820
2006 CCL19/CCL21 promote activation-induced cell death (AICD) of antigen-responding CD4+ T cells during the clonal contraction phase, partially through enhancing Fas ligand expression; plt/plt mice lacking CCL19/CCL21 show prolonged T cell expansion and impaired AICD. OVA/CFA immunization of plt/plt and wild-type mice, in vivo tracking of OVA-responding T cells, in vitro AICD assay with anti-CD3/CD28, Fas ligand expression analysis Blood High 16973962
2013 CCL19/CCR7 signaling in A549 lung cancer cells upregulates heparanase expression via transcription factor Sp1; Sp1 binds to the heparanase gene promoter (ChIP assay), and this pathway promotes tumor cell invasion. Recombinant CCL19 stimulation, CCR7 blockade, Sp1 siRNA, chromatin immunoprecipitation (ChIP), qPCR/Western blot, Transwell invasion assay Tumour biology Medium 23649655
2009 PGE2 induces CCR7 expression on human monocytes and enables migration to CCL19 and CCL21 via EP2/EP4 receptor engagement, cAMP elevation, and the cAMP/PKA pathway; p38 MAPK is required for CCR7 mRNA transcription; transcription factors CREB-1, C/EBPα, and C/EBPβ translocate to the nucleus and bind the CCR7 promoter following PGE2 stimulation. PGE2 stimulation of human monocytes, cAMP measurement, PKA/p38/MAPK pathway inhibitors, transcription factor nuclear translocation and promoter binding assays, migration assay Molecular immunology Medium 19545899
2010 PGE2-matured DCs have high surface CCR7 but suppressed CCL19 production; this suppression reduces their ability to attract naive T cells. TLR ligand/IFN-matured DCs produce high CCL19 but have lower surface CCR7 due to auto-internalization in the CCL19-rich maturation environment. DC maturation protocols, CCL19 ELISA, CCR7 surface staining, in vitro migration assay for naive T cells, in vivo DC tracking with 111In-labeled DCs Blood High 20498301
2018 CCL19 inhibits colorectal cancer angiogenesis through a CCR7-dependent mechanism involving upregulation of miR-206, which suppresses the Met/ERK/Elk-1/HIF-1α/VEGF-A pathway. Stable CCL19 overexpression/shRNA lentiviral transduction, HUVEC CCR7 shRNA knockdown, HUVEC proliferation/migration/sprouting assays, in vivo angiogenesis mouse model, pathway Western blot Cell death & disease Medium 30250188
2015 CCL19/CCR7 signaling in ovarian cancer cells promotes epithelial-to-mesenchymal transition (EMT) via ERK signaling, mediated through the adapter protein CrkL; CrkL knockdown suppresses CCL19-stimulated p-ERK and EMT markers (N-cadherin, Snail, MMP9) and reduces invasion, without affecting p-AKT. CrkL siRNA knockdown in SKOV-3 cells, Western blot for signaling molecules and EMT markers, Transwell invasion and wound healing assays Medical oncology Medium 25636509
2017 CCL19/CCR7 interaction in endometrial stromal cells activates PI3K/Akt signaling and upregulates Bcl2, MMP2, and MMP9, thereby promoting ESC proliferation and invasion contributing to endometriosis pathogenesis. ELISA of peritoneal fluid, cell proliferation and Transwell invasion assays, Western blot for p-AKT/Bcl2/MMP2/MMP9 American journal of reproductive immunology Medium 28856757
2014 CCL19/CCR7 interaction in bone marrow stromal cells (BMSCs) upregulates MMP9 via PI3K/Akt pathway, promoting BMSC migration; LY294002 (PI3K inhibitor) abolishes CCL19-induced Akt phosphorylation and MMP9 upregulation. Transwell migration assay, Western blot, real-time PCR, LY294002 pharmacological inhibition Biochemical and biophysical research communications Medium 25086360
2011 Seminal fluid induces expression of CCL19 in uterine glandular and luminal epithelial cells, and CCL19 acts through CCR7 to recruit FOXP3+ regulatory T cells to the uterus prior to embryo implantation; both seminal plasma and sperm are required for maximal CCL19 expression. Flow cytometry, immunohistochemistry, qPCR, mating with seminal vesicle-deficient males Biology of reproduction Medium 21389340
2019 CCL19-expressing astrocytes are required for gliosis-induced CNS lymphoma development; CCL19 from astrocytes retains CCR7+ lymphoma cells in brain parenchyma, and deletion of CCL19 in mice or CCR7 from lymphoma cells abrogates CNS lymphoma formation. CCL19-deleted mice, CCR7-deleted lymphoma cells, two-photon microscopy, xenograft models Cancer cell High 31526758
2024 CCL19-secreting fibroblasts facilitate lymphocyte trafficking to tertiary lymphoid structures (TLSs) in colorectal cancer liver metastasis; CCL19 treatment promotes TLS neogenesis and prevents tumor growth in mice. Single-cell RNA-seq, spatial transcriptomics (Stereo-seq), in vitro monoclonal antibody generation from TLS plasma cells, in vivo CCL19 treatment in humanized mouse model Cancer cell High 39137726
2001 Neutrophils produce biologically active CCL20 and CCL19 (MIP-3β) upon LPS or TNF-α stimulation; neutrophil supernatants induce chemotaxis of immature and mature DCs and trigger CCR7-expressing lymphocyte adhesion to ICAM-1, effects abolished by anti-CCL19 neutralizing antibodies. LPS/TNF-α stimulation of neutrophils, chemotaxis assay, integrin-dependent adhesion assay, neutralizing antibodies European journal of immunology Medium 11449350
1998 CCL19 (ELC) is a high-affinity ligand for CCR7 on lymphocytes; CCL19 induces calcium mobilization and chemotaxis of CD4+, CD8+ T cells, and B cells but not NK cells, monocytes, or neutrophils; CCR7 mRNA is dramatically upregulated in T cells upon IL-2 or PHA+IL-2 stimulation; CCL19 and CCR7 co-localize in parafollicular regions of lymph nodes by ISH. ELC-SEAP fusion protein binding assay, calcium mobilization, chemotaxis assay, RT-PCR, in situ hybridization International immunology High 9701028
2023 CCL19 promotes TH2 cell differentiation in allergic airway disease; recombinant CCL19 increases STAT5 phosphorylation and upregulates TH2- and IL-2-associated genes in naive CD4+ T cells; Ccl19-deficient mice show reduced allergic inflammation, less IL-4/IL-13 production, and attenuated airway hyperresponsiveness. Ccl19-deficient mice in OVA asthma model, co-culture of naive CD4+ T cells with Ccl19-deficient DCs or FRCs, recombinant CCL19 stimulation, STAT5 phosphorylation by flow cytometry, RNA-seq The Journal of allergy and clinical immunology High 37956733

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2018 IL-7 and CCL19 expression in CAR-T cells improves immune cell infiltration and CAR-T cell survival in the tumor. Nature biotechnology 634 29505028
2000 Coexpression of the chemokines ELC and SLC by T zone stromal cells and deletion of the ELC gene in the plt/plt mouse. Proceedings of the National Academy of Sciences of the United States of America 457 11070085
2000 The leukotriene C(4) transporter MRP1 regulates CCL19 (MIP-3beta, ELC)-dependent mobilization of dendritic cells to lymph nodes. Cell 353 11114332
2001 The CCR7 ligand elc (CCL19) is transcytosed in high endothelial venules and mediates T cell recruitment. The Journal of experimental medicine 275 11342595
2021 IL-7 and CCL19-secreting CAR-T cell therapy for tumors with positive glypican-3 or mesothelin. Journal of hematology & oncology 245 34325726
2013 A myriad of functions and complex regulation of the CCR7/CCL19/CCL21 chemokine axis in the adaptive immune system. Cytokine & growth factor reviews 237 23587803
2007 CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 200 17881634
2003 CCL19/CCL21-triggered signal transduction and migration of dendritic cells requires prostaglandin E2. Blood 193 14592837
2011 Seminal fluid regulates accumulation of FOXP3+ regulatory T cells in the preimplantation mouse uterus through expanding the FOXP3+ cell pool and CCL19-mediated recruitment. Biology of reproduction 179 21389340
2011 Dendritic cell chemotaxis in 3D under defined chemokine gradients reveals differential response to ligands CCL21 and CCL19. Proceedings of the National Academy of Sciences of the United States of America 164 21422278
2016 Common and biased signaling pathways of the chemokine receptor CCR7 elicited by its ligands CCL19 and CCL21 in leukocytes. Journal of leukocyte biology 155 26729814
2002 Functional expression of the lymphoid chemokines CCL19 (ELC) and CCL 21 (SLC) at the blood-brain barrier suggests their involvement in G-protein-dependent lymphocyte recruitment into the central nervous system during experimental autoimmune encephalomyelitis. European journal of immunology 155 12209625
2019 CCL19 and CCR7 Expression, Signaling Pathways, and Adjuvant Functions in Viral Infection and Prevention. Frontiers in cell and developmental biology 154 31632965
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
2001 Neutrophils produce biologically active macrophage inflammatory protein-3alpha (MIP-3alpha)/CCL20 and MIP-3beta/CCL19. European journal of immunology 136 11449350
2011 Characterization of CCL19 and CCL21 in rheumatoid arthritis. Arthritis and rheumatism 124 21225692
2006 The chemokine receptor CCX-CKR mediates effective scavenging of CCL19 in vitro. European journal of immunology 123 16791897
2003 Lymphoid chemokines CCL19 and CCL21 are expressed in the central nervous system during experimental autoimmune encephalomyelitis: implications for the maintenance of chronic neuroinflammation. Brain pathology (Zurich, Switzerland) 123 12580544
2018 CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer. Cell death & disease 122 30250188
2007 CCL19 is constitutively expressed in the CNS, up-regulated in neuroinflammation, active and also inactive multiple sclerosis lesions. Journal of neuroimmunology 109 17825430
2024 CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis. Cancer cell 108 39137726
2001 The T cell chemokine receptor CCR7 is internalized on stimulation with ELC, but not with SLC. European journal of immunology 105 11745346
2010 PGE(2) transiently enhances DC expression of CCR7 but inhibits the ability of DCs to produce CCL19 and attract naive T cells. Blood 102 20498301
2000 The CC chemokine CK beta-11/MIP-3 beta/ELC/Exodus 3 mediates tumor rejection of murine breast cancer cells through NK cells. Journal of immunology (Baltimore, Md. : 1950) 102 10754294
1999 Expression and cellular localization of the CC chemokines PARC and ELC in human atherosclerotic plaques. The American journal of pathology 93 10027395
1998 EBI1-ligand chemokine (ELC) attracts a broad spectrum of lymphocytes: activated T cells strongly up-regulate CCR7 and efficiently migrate toward ELC. International immunology 85 9701028
2010 CCL21 is sufficient to mediate DC migration, maturation and function in the absence of CCL19. European journal of immunology 78 20201039
2008 Arrestin 3 mediates endocytosis of CCR7 following ligation of CCL19 but not CCL21. Journal of immunology (Baltimore, Md. : 1950) 76 18802075
2021 The BCMA-Targeted Fourth-Generation CAR-T Cells Secreting IL-7 and CCL19 for Therapy of Refractory/Recurrent Multiple Myeloma. Frontiers in immunology 73 33767695
2018 CCL19-producing fibroblastic stromal cells restrain lung carcinoma growth by promoting local antitumor T-cell responses. The Journal of allergy and clinical immunology 72 29391257
1999 CCR7 ligands, SLC/6Ckine/Exodus2/TCA4 and CKbeta-11/MIP-3beta/ELC, are chemoattractants for CD56(+)CD16(-) NK cells and late stage lymphoid progenitors. Cellular immunology 72 10222066
2003 EBV-induced molecule 1 ligand chemokine (ELC/CCL19) promotes IFN-gamma-dependent antitumor responses in a lung cancer model. Journal of immunology (Baltimore, Md. : 1950) 70 14662845
2016 ACKR4 on Stromal Cells Scavenges CCL19 To Enable CCR7-Dependent Trafficking of APCs from Inflamed Skin to Lymph Nodes. Journal of immunology (Baltimore, Md. : 1950) 60 26976955
2016 Mutations in NOTCH1 PEST domain orchestrate CCL19-driven homing of chronic lymphocytic leukemia cells by modulating the tumor suppressor gene DUSP22. Leukemia 58 28017968
2006 Loss of dendritic cell migration and impaired resistance to Leishmania donovani infection in mice deficient in CCL19 and CCL21. Journal of immunology (Baltimore, Md. : 1950) 57 16622017
2013 Global chemokine expression in systemic sclerosis (SSc): CCL19 expression correlates with vascular inflammation in SSc skin. Annals of the rheumatic diseases 55 23873879
2009 CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B. Immunology 54 20002784
2004 CCL19 and CXCL12 trigger in vitro chemotaxis of human mantle cell lymphoma B cells. Clinical cancer research : an official journal of the American Association for Cancer Research 54 14871974
2016 Baicalin attenuates inflammation in mice with OVA-induced asthma by inhibiting NF-κB and suppressing CCR7/CCL19/CCL21. International journal of molecular medicine 52 27666000
2013 Inhibition of CCR7/CCL19 axis in lesional skin is a critical event for clinical remission induced by TNF blockade in patients with psoriasis. The American journal of pathology 52 23731727
2021 Enhanced anti-tumor efficacy of IL-7/CCL19-producing human CAR-T cells in orthotopic and patient-derived xenograft tumor models. Cancer immunology, immunotherapy : CII 51 33559069
2019 Powerful Anticolon Tumor Effect of Targeted Gene Immunotherapy Using Folate-Modified Nanoparticle Delivery of CCL19 To Activate the Immune System. ACS central science 51 30834316
2003 Differential expression of CCL19 by DC-Lamp+ mature dendritic cells in human lymph node versus chronically inflamed skin. The Journal of pathology 48 12474232
2023 GPC3-IL7-CCL19-CAR-T primes immune microenvironment reconstitution for hepatocellular carcinoma therapy. Cell biology and toxicology 47 37853185
2022 Does CCL19 act as a double-edged sword in cancer development? Clinical and experimental immunology 47 35020885
2008 CXCL13 is highly produced by Sézary cells and enhances their migratory ability via a synergistic mechanism involving CCL19 and CCL21 chemokines. Cancer research 47 18757429
2022 Development of Nectin4/FAP-targeted CAR-T cells secreting IL-7, CCL19, and IL-12 for malignant solid tumors. Frontiers in immunology 46 36479116
2009 CCR7-specific migration to CCL19 and CCL21 is induced by PGE(2) stimulation in human monocytes: Involvement of EP(2)/EP(4) receptors activation. Molecular immunology 46 19545899
2019 Accumulation of Circulating CCR7+ Natural Killer Cells Marks Melanoma Evolution and Reveals a CCL19-Dependent Metastatic Pathway. Cancer immunology research 43 30940644
2007 Regulatory role of lymphoid chemokine CCL19 and CCL21 in the control of allergic rhinitis. Journal of immunology (Baltimore, Md. : 1950) 43 17947663
2013 CCL19, a B cell chemokine, is related to the decrease of blood memory B cells and predicts the clinical response to rituximab in patients with rheumatoid arthritis. Arthritis and rheumatism 42 23740460
2006 Role of CCL21 and CCL19 in allergic inflammation in the ovalbumin-specific murine asthmatic model. The Journal of allergy and clinical immunology 41 16675330
2014 Contribution of homeostatic chemokines CCL19 and CCL21 and their receptor CCR7 to coronary artery disease. Arteriosclerosis, thrombosis, and vascular biology 40 24990231
2013 CCL19/CCR7 upregulates heparanase via specificity protein-1 (Sp1) to promote invasion of cell in lung cancer. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 23649655
2009 Macrophages participate in lymphangiogenesis in idiopathic diffuse alveolar damage through CCL19-CCR7 signal. Human pathology 40 19540558
2023 CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science immunology 39 37656776
2018 Adipose tissue expression of CCL19 chemokine is positively associated with insulin resistance. Diabetes/metabolism research and reviews 38 30339734
2017 Ischemic stroke damages the intestinal mucosa and induces alteration of the intestinal lymphocytes and CCL19 mRNA in rats. Neuroscience letters 38 28859865
2006 CCL19-IgG prevents allograft rejection by impairment of immune cell trafficking. Journal of the American Society of Nephrology : JASN 37 16899521
2015 Crk-like adapter protein regulates CCL19/CCR7-mediated epithelial-to-mesenchymal transition via ERK signaling pathway in epithelial ovarian carcinomas. Medical oncology (Northwood, London, England) 36 25636509
2019 Age-Related Gliosis Promotes Central Nervous System Lymphoma through CCL19-Mediated Tumor Cell Retention. Cancer cell 35 31526758
2015 Protection from diet-induced obesity and insulin resistance in mice lacking CCL19-CCR7 signaling. Obesity (Silver Spring, Md.) 35 26097021
2010 Role of the atypical chemoattractant receptor CRAM in regulating CCL19 induced CCR7 responses in B-cell chronic lymphocytic leukemia. Molecular cancer 35 21092185
2005 Evidence for an enhanced adhesion of DC to fibronectin and a role of CCL19 and CCL21 in the accumulation of DC around the pre-diabetic islets in NOD mice. European journal of immunology 34 16047341
2023 CCL19+ dendritic cells potentiate clinical benefit of anti-PD-(L)1 immunotherapy in triple-negative breast cancer. Med (New York, N.Y.) 33 37201522
2019 The effects of CCL3, CCL4, CCL19 and CCL21 as molecular adjuvants on the immune response to VAA DNA vaccine in flounder (Paralichthys olivaceus). Developmental and comparative immunology 33 31494219
2017 Increased CCL19 expression is associated with progression in cervical cancer. Oncotarget 33 29088748
2015 Solution Structure of CCL19 and Identification of Overlapping CCR7 and PSGL-1 Binding Sites. Biochemistry 33 26115234
2010 Klebsiella pneumoniae-triggered DC recruit human NK cells in a CCR5-dependent manner leading to increased CCL19-responsiveness and activation of NK cells. European journal of immunology 33 20865789
2002 Migration of Salmonella typhimurium --harboring bone marrow--derived dendritic cells towards the chemokines CCL19 and CCL21. Microbial pathogenesis 33 12071677
2015 Differential ligand-signaling network of CCL19/CCL21-CCR7 system. Database : the journal of biological databases and curation 32 26504105
2014 Inhibition of chemokine (C-C motif) receptor 7 sialylation suppresses CCL19-stimulated proliferation, invasion and anti-anoikis. PloS one 32 24915301
2009 Homeostatic chemokines CCL19 and CCL21 promote inflammation in human immunodeficiency virus-infected patients with ongoing viral replication. Clinical and experimental immunology 32 19664149
2003 Expression of macrophage inflammatory protein-3 beta/CCL19 in pulmonary sarcoidosis. American journal of respiratory and critical care medicine 32 12626344
2016 HIV integration and the establishment of latency in CCL19-treated resting CD4(+) T cells require activation of NF-κB. Retrovirology 30 27459960
2004 Inhibition of generation of cytotoxic T lymphocyte activity by a CCL19/macrophage inflammatory protein (MIP)-3beta antagonist. The Journal of biological chemistry 30 15231820
2020 CCL19 suppresses gastric cancer cell proliferation, migration, and invasion through the CCL19/CCR7/AIM2 pathway. Human cell 29 32564199
2020 Local injection of CCL19-expressing mesenchymal stem cells augments the therapeutic efficacy of anti-PD-L1 antibody by promoting infiltration of immune cells. Journal for immunotherapy of cancer 29 32675195
2017 Newcastle disease virus-like particles induce DC maturation through TLR4/NF-κB pathway and facilitate DC migration by CCR7-CCL19/CCL21 axis. Veterinary microbiology 29 28619138
2007 CCL19 (ELC) as an adjuvant for DNA vaccination: induction of a TH1-type T-cell response and enhancement of antitumor immunity. Cancer gene therapy 29 17384577
2006 Mature monocyte-derived dendritic cells respond more strongly to CCL19 than to CXCL12: consequences for directional migration. Immunology 29 16423060
2024 Safety and feasibility of anti-CD19 CAR T cells expressing inducible IL-7 and CCL19 in patients with relapsed or refractory large B-cell lymphoma. Cell discovery 28 38191529
2012 CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC. Cancer gene therapy 28 23099886
2006 Dendritic cells express CCR7 and migrate in response to CCL19 (MIP-3beta) after exposure to Helicobacter pylori. Microbes and infection 28 16500130
2021 CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance. Journal of gastroenterology 27 34218330
2019 Elevated CCL19/CCR7 Expression During the Disease Process of Primary Sjögren's Syndrome. Frontiers in immunology 27 31068931
2017 A Novel Computational Model Predicts Key Regulators of Chemokine Gradient Formation in Lymph Nodes and Site-Specific Roles for CCL19 and ACKR4. Journal of immunology (Baltimore, Md. : 1950) 27 28807994
2016 Epicatechin downregulates adipose tissue CCL19 expression and thereby ameliorates diet-induced obesity and insulin resistance. Nutrition, metabolism, and cardiovascular diseases : NMCD 27 28062181
2014 CCL19 and CCL21 modulate the inflammatory milieu in atherosclerotic lesions. Drug design, development and therapy 27 25473269
2023 Chemokine CCL19 promotes type 2 T-cell differentiation and allergic airway inflammation. The Journal of allergy and clinical immunology 26 37956733
2017 CCL19/CCR7 contributes to the pathogenesis of endometriosis via PI3K/Akt pathway by regulating the proliferation and invasion of ESCs. American journal of reproductive immunology (New York, N.Y. : 1989) 26 28856757
2017 CK12a, a CCL19-like Chemokine That Orchestrates both Nasal and Systemic Antiviral Immune Responses in Rainbow Trout. Journal of immunology (Baltimore, Md. : 1950) 26 29061765
2012 CCR7/CCL19 controls expression of EDG-1 in T cells. The Journal of biological chemistry 26 22334704
2018 Fluorescently Tagged CCL19 and CCL21 to Monitor CCR7 and ACKR4 Functions. International journal of molecular sciences 25 30518137
2016 Graft Site Microenvironment Determines Dendritic Cell Trafficking Through the CCR7-CCL19/21 Axis. Investigative ophthalmology & visual science 25 27031839
2014 Matrix metalloproteinase-9 is up-regulated by CCL19/CCR7 interaction via PI3K/Akt pathway and is involved in CCL19-driven BMSCs migration. Biochemical and biophysical research communications 25 25086360
2013 IL-18-based combinatorial adjuvants promote the intranodal production of CCL19 by NK cells and dendritic cells of cancer patients. Oncoimmunology 25 24228233
2009 CCR7+ myeloid dendritic cells together with CCR7+ T cells and CCR7+ macrophages invade CCL19+ nonnecrotic muscle fibers in inclusion body myositis. Journal of the neurological sciences 25 19171354
2006 Chemokines CCL19 and CCL21 promote activation-induced cell death of antigen-responding T cells. Blood 25 16973962
2020 MiR-325-3p inhibits renal inflammation and fibrosis by targeting CCL19 in diabetic nephropathy. Clinical and experimental pharmacology & physiology 24 32603491