Affinage

CCL26

C-C motif chemokine 26 · UniProt Q9Y258

Length
94 aa
Mass
10.6 kDa
Annotated
2026-06-09
100 papers in source corpus 36 papers cited in narrative 37 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL26 (eotaxin-3) is a secreted CC chemokine that orchestrates Th2-type leukocyte trafficking and resolution by engaging multiple chemokine receptors with opposing functional outcomes (PMID:10488147, PMID:20974991). It is a high-affinity functional agonist of CCR3, mobilizing calcium, driving actin polymerization, and chemoattracting eosinophils and basophils (PMID:10488147, PMID:11286614), and it additionally acts as a functional agonist of the fractalkine receptor CX3CR1, recruiting CD16+ NK cells, effector CD8+ T cells, and CD14low CD16high monocytes (PMID:20974991, PMID:23414540). In parallel, CCL26 binds CCR1, CCR2, and CCR5 without activating them and instead behaves as a natural antagonist that suppresses responses to their cognate agonists and can drive Gi-dependent chemorepulsion of monocytes (PMID:12689946, PMID:15039444). Beyond receptor signaling, CCL26 has direct bactericidal activity against airway pathogens through its cationic, amphipathic C-terminus, and mast-cell chymase/tryptase cleavage separates an antibacterial C-terminal fragment from an LPS-neutralizing N-terminal fragment (PMID:25377782). CCL26 expression is induced by the Th2 cytokines IL-4 and IL-13 through the JAK1/JAK2–STAT6 axis acting on a proximal STAT6 promoter element, with full transcriptional output requiring CBP–STAT6 complex formation, histone H3 acetylation, and promoter CpG demethylation adjacent to a CRE site (PMID:16045735, PMID:22226123, PMID:21325281, PMID:24323578). Its induction is further gated by a nongastric H+,K+-ATPase (ATP12A) and intracellular calcium signaling, which is why proton-pump inhibitors block CCL26 in epithelial cells (PMID:27717558, PMID:33581123, PMID:23185525). Functionally, surface-bound CCL26 on IL-4-stimulated airway epithelium mediates eosinophil transepithelial migration via CCR3 (PMID:16983721), while epithelial CCL26 also drives resolution of allergic eosinophilia by activating CX3CR1+ macrophages to secrete C1q and clear eosinophils (PMID:36790376). CCL26 additionally promotes migration and invasion of non-immune cells including fibroblasts, trophoblasts, and tumor cells (PMID:20143648, PMID:23477905, PMID:29051319).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1999 High

    Established CCL26 as a bona fide functional chemokine by showing it is an agonist of CCR3, defining its primary receptor and eosinophil/basophil-recruiting role.

    Evidence Calcium flux, radioligand competition binding, and chemotaxis with recombinant baculovirus-expressed protein on CCR3+ cells and primary leukocytes

    PMID:10488147

    Open questions at the time
    • No structural basis for receptor selectivity addressed
    • In vivo relevance not yet tested
  2. 2001 High

    Defined the 3D fold and dynamics of CCL26, linking flexible N-terminal/N-loop regions to receptor binding and activation.

    Evidence NMR structure determination with 15N relaxation backbone dynamics

    PMID:11425309

    Open questions at the time
    • No co-structure with any receptor
    • Functional consequences of dynamic regions inferred, not mutated
  3. 2001 Medium

    Showed CCL26 is constitutively and IL-4-inducibly expressed by dermal fibroblasts and is equipotent with other eotaxins for chemotaxis but weaker for ROS release, hinting at signaling biases.

    Evidence RT-PCR, chemotaxis, actin polymerization, ROS, and calcium assays in primary fibroblasts

    PMID:11286614

    Open questions at the time
    • Mechanism of reduced ROS efficacy unexplained
    • Single cell type
  4. 2003 High

    Revealed CCL26 as a multi-receptor regulator that antagonizes CCR2 and drives monocyte chemorepulsion, distinguishing it functionally from canonical agonist chemokines.

    Evidence Calcium, ERK, enzyme-release, and chemorepulsion assays with pertussis toxin blockade in transfected cells and monocytes

    PMID:12689946

    Open questions at the time
    • Structural basis of antagonism vs agonism not resolved
    • In vivo significance of chemorepulsion untested
  5. 2004 High

    Extended CCL26's antagonist role to CCR1 and CCR5 and mapped distinct structural epitopes for its multiple receptor interactions.

    Evidence Radioligand binding, chemotaxis, calcium, actin assays in transfected cells plus 3D model epitope analysis

    PMID:15039444

    Open questions at the time
    • Epitopes predicted from model, not co-crystallized
    • No mutational confirmation of epitope assignments
  6. 2004 High

    Established the JAK–STAT6 and MEK/ERK pathways and a proximal STAT6 promoter element as the core IL-4/IL-13 induction machinery for CCL26, distinguishing its regulation from eotaxin-1.

    Evidence Promoter deletion/mutagenesis, dominant-negative STAT6, JAK/MEK/p38/NF-κB inhibitors, signaling readouts across fibroblasts, epithelium, and keratinocytes

    PMID:15231490 PMID:15521376 PMID:16045735 PMID:16755001

    Open questions at the time
    • Cell-type-specific NF-κB effects unexplained
    • Quantitative contribution of ERK vs STAT6 unclear
  7. 2005 High

    Demonstrated that surface-bound CCL26 on IL-4-stimulated epithelium is the operative form driving eosinophil transepithelial migration via CCR3, and that CCL26 autoregulates via CCR3.

    Evidence Transepithelial chemotaxis with antibody blockade, confocal surface localization, CCR3 antagonist and flow cytometry autoregulation studies

    PMID:15863444 PMID:16983721

    Open questions at the time
    • Relative contribution of GAG vs protein anchoring not quantified
    • In vivo membrane-bound role untested
  8. 2010 High

    Identified CCL26 as a functional CX3CR1 agonist, broadening its target leukocyte repertoire to NK cells, effector T cells, and patrolling monocytes.

    Evidence Calcium flux, competition binding, in vitro and in vivo chemotaxis, HUVEC adhesion assays with human (not mouse) CX3CR1

    PMID:20974991

    Open questions at the time
    • Species selectivity (human vs mouse CX3CR1) mechanistically unexplained
    • Structural basis of CX3CR1 engagement unknown
  9. 2011 High

    Defined epigenetic control of CCL26 transcription, showing CBP–STAT6 complex formation, histone H3 acetylation, and a required CRE site for full IL-13-induced output.

    Evidence ChIP, promoter-reporter, CBP siRNA, and HDAC inhibitor assays

    PMID:21325281

    Open questions at the time
    • Stimulus-specific CBP recruitment kinetics not detailed
    • Interplay with other coactivators unmapped
  10. 2013 High

    Connected CCL26 expression to promoter DNA methylation, showing CpG demethylation near the CRE site permits CBP/ATF-2 binding and elevated expression in allergic tissue.

    Evidence Bisulfite sequencing, methylation-free promoter reporters, 5-azacytidine treatment, and EMSA

    PMID:24323578

    Open questions at the time
    • Enzymes driving demethylation in allergic tissue unidentified
    • Causality in patients correlational
  11. 2015 High

    Uncovered a receptor-independent innate immune function of CCL26 as a direct bactericidal peptide and a protease-cleaved generator of distinct antibacterial and LPS-neutralizing fragments.

    Evidence Viable count, electron microscopy, membrane permeabilization, chymase/tryptase cleavage, LPS neutralization, and CCR3 activation assays

    PMID:25377782

    Open questions at the time
    • In vivo antimicrobial relevance untested
    • Physiological abundance of cleaved fragments unknown
  12. 2016 High

    Identified the nongastric H+,K+-ATPase ATP12A and intracellular calcium as required upstream regulators of Th2-cytokine-induced CCL26, explaining proton-pump-inhibitor responsiveness.

    Evidence ATP12A siRNA knockdown, intracellular pH imaging, K+ manipulation, calcium imaging, and PPI/SCH-28080 treatment in epithelial and EoE cells

    PMID:23185525 PMID:27717558 PMID:33581123

    Open questions at the time
    • Molecular link between H+/K+ exchange and STAT6-driven transcription incomplete
    • Tissue specificity of PPI effect (epithelium vs fibroblasts) unexplained
  13. 2018 Medium

    Mapped negative feedback regulators of CCL26, with CISH and IFN-γ/STAT1 dampening STAT6-driven expression.

    Evidence Microarray, reciprocal siRNA/overexpression of CISH, and STAT1/STAT6 readouts in fibroblasts and myofibroblasts

    PMID:20059579 PMID:23607908 PMID:30197185

    Open questions at the time
    • Relative weight of feedback regulators in vivo unknown
    • Mechanism of CISH action on STAT6 not detailed
  14. 2019 High

    Added 15-lipoxygenase-1/ERK as an amplifying input to IL-13-induced CCL26 in nasal epithelium, integrating lipid metabolism into chemokine induction.

    Evidence ALOX15 DsiRNA, enzymatic and ERK inhibitors with phospho-ERK and CCL26 readouts in air-liquid interface cultures

    PMID:31301373

    Open questions at the time
    • 15LO1 metabolite linking to ERK not identified
    • Restricted to nasal epithelium
  15. 2023 High

    Established an in vivo resolution function for epithelial CCL26, which activates CX3CR1+ macrophages to secrete C1q and clear eosinophils, resolving allergic lung inflammation.

    Evidence Conditional epithelial CCL26 knockout and CX3CR1-macrophage depletion in mice, scRNA-seq, mass cytometry, binding assays, and human bronchoprovocation

    PMID:36790376

    Open questions at the time
    • Mechanism of C1q-mediated eosinophil clearance not fully dissected
    • Whether membrane-bound vs soluble CCL26 mediates macrophage activation unclear
  16. 2021 Medium

    Extended CCL26 function to non-immune migration and tumor biology, promoting fibroblast/trophoblast/tumor cell invasion via CCR3-TAM crosstalk and PI3K/AKT/mTOR signaling.

    Evidence Invasion/migration assays, MMP2 zymography, CCR3 co-culture calcium signaling, PI3K/AKT/mTOR Western blots, and in vivo tumor models

    PMID:20143648 PMID:23477905 PMID:29051319 PMID:33764366

    Open questions at the time
    • Receptor mediating tumor-cell-intrinsic PI3K/AKT signaling not defined
    • In vivo causality for invasion limited to single models

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how CCL26's structural features dictate the switch between agonism (CCR3, CX3CR1) and antagonism (CCR1/2/5), and how membrane-bound versus soluble forms partition between recruitment and resolution functions.
  • No receptor co-structures
  • No structure-guided mutants tested across the full receptor panel
  • Membrane vs soluble functional partitioning undefined in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0098772 molecular function regulator activity 2 GO:0090729 toxin activity 1
Localization
GO:0005576 extracellular region 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
CCR1CCR2CCR3CCR5CX3CR1

Evidence

Reading pass · 37 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CCL26 (eotaxin-3) is a functional agonist ligand for CCR3; recombinant CCL26 induced calcium mobilization in CCR3-expressing L1.2 cells (EC50 ~3 nM), competed with 125I-eotaxin for CCR3 binding (IC50 ~13 nM), and was chemotactic for peripheral blood eosinophils and basophils. Calcium mobilization assay, radioligand competition binding, chemotaxis assay using recombinant protein from baculovirus expression system The Journal of Biological Chemistry High 10488147
2001 The 3D solution structure of CCL26 was determined by NMR; it is monomeric and adopts the canonical chemokine fold (unstructured N-terminus, N-loop, 310-helix, three-stranded antiparallel β-sheet, C-terminal α-helix). Backbone dynamics revealed large-amplitude motions in the N-terminus, N-loop, and β1-β2 turn, suggesting these regions contribute to receptor binding and activation. NMR spectroscopy (structure determination + 15N relaxation backbone dynamics) Biochemistry High 11425309
2001 CCL26 is expressed as mRNA in human dermal fibroblasts constitutively and is upregulated by IL-4 and IL-4 + TNF-α; at equimolar concentrations CCL26 showed the same efficacy as eotaxin and eotaxin-2 for eosinophil chemotaxis and actin polymerization (cytoskeletal rearrangement via CCR3/Gi), but lower efficacy for release of toxic reactive oxygen species. LightCycler RT-PCR, chemotaxis assay (Boyden chamber), actin polymerization assay, ROS release assay, calcium flux assay The Journal of Investigative Dermatology Medium 11286614
2002 CCL26 mRNA expression in human lung epithelial cells and dermal fibroblasts is induced by IL-4 and IL-13 in a time- and dose-dependent manner; IL-4 shows ~100-fold greater potency than IL-13. TNF-α alone does not induce CCL26 but synergizes with IL-4/IL-13. Dexamethasone pre-treatment diminishes induction. Northern blot hybridization Cytokine Medium 12061839
2002 CCL26 directly stimulates superoxide anion generation and degranulation (eosinophil peroxidase release) in eosinophil-like HL-60 cells via CCR3; these responses are blocked by anti-CCL26 antibody or anti-CCR3 antibody pre-treatment. Superoxide anion assay, eosinophil peroxidase degranulation assay, neutralizing antibody blockade Experimental Biology and Medicine Medium 12192108
2003 CCL26 binds to CCR2 on monocytes and CCR2-transfected cells but, unlike CCL2/MCP-1, does not trigger intracellular calcium mobilization, enzyme release, or ERK phosphorylation; instead it inhibits CCL2-mediated responses, acting as a natural CCR2 antagonist. CCL26 also promoted active repulsion (chemorepulsion) of monocytes away from a CCL26 gradient, an effect amplified by a co-gradient of CCL2 and abolished by pertussis toxin (Gi-dependent). CCL26 was expressed by vascular endothelial cells and was essential for eosinophil transendothelial migration. Calcium mobilization assay, enzyme release assay, ERK phosphorylation (Western blot), chemotaxis/chemorepulsion assay (Boyden chamber), pertussis toxin blockade, transfected cell lines Blood High 12689946
2003 CCL26 is produced by bronchial epithelial cells, and its production is upregulated by IL-4 and IL-13 and attenuated by IFN-γ and glucocorticoids, paralleling regulation of eotaxin-1 but with distinct kinetics. Immunohistochemistry (tissue), ELISA (cell culture supernatants), in vitro cytokine stimulation Cellular Immunology Medium 14698143
2004 CCL26 acts as a natural antagonist for CCR1 and CCR5: it binds CCR1- and CCR5-transfected cells and to monocytes expressing both receptors, and inhibits chemotaxis, calcium release, and actin polymerization induced by known CCR1/CCR5 agonists. 3D structural analysis identified two distinct epitopes potentially responsible for binding CCR1, CCR2, CCR3, and CCR5. Radioligand binding (transfected cells), chemotaxis assay, calcium mobilization assay, actin polymerization assay, structural analysis of 3D model The Journal of Biological Chemistry High 15039444
2004 IL-4-induced CCL26 production in human lung fibroblasts (HFL-1) is regulated by the STAT6 and MEK/ERK pathways; eotaxin-3/CCL26 production is inhibited by MEK inhibitors (PD98059, U0126) and the p38 MAPK inhibitor SB203580, and is less sensitive to NF-κB inhibition than eotaxin-1 production. ELISA, RT-PCR, kinase inhibitor treatment (MEK, p38, NF-κB pathway inhibitors) Biological & Pharmaceutical Bulletin Medium 16755001
2004 IL-4-induced CCL26 production in bronchial epithelial cells (BEAS-2B) is mediated through STAT6 signaling downstream of the type 2 IL-4 receptor; NF-κB inhibition enhanced (rather than inhibited) CCL26 gene expression, in contrast to eotaxin-1. ELISA, RT-PCR, flow cytometry (receptor expression), Western blot (STAT6 phosphorylation), NF-κB inhibitor treatment Annals of Allergy, Asthma & Immunology Medium 15521376
2004 Concurrent IFN-γ treatment inhibits Th2 cytokine-induced CCL26 production in bronchial epithelial cells by downregulating STAT6 activation; however, 2-day pre-treatment with IFN-γ paradoxically enhances IL-4/IL-13-induced CCL26 production by upregulating IL-4Rα and IL-2Rγ expression. ELISA, RT-PCR, Western blot (STAT6 phosphorylation), dose/time-dependent cytokine treatment American Journal of Respiratory Cell and Molecular Biology Medium 15231490
2005 IL-4 induces CCL26 production in human keratinocytes (HaCaT cells) via the JAK1/JAK2–STAT6 pathway; the proximal STAT6-binding site in the CCL26 promoter is the key response element. TNF-α synergizes with IL-4. Dexamethasone, IFN-γ, p38 MAPK inhibitor (SB202190), leflunomide, and JAK inhibitor 1 (but not JAK3 inhibitor) suppress IL-4-induced CCL26 production, implicating JAK1/JAK2 and the type 2 IL-4 receptor. ELISA, RT-PCR, 5′ promoter deletion constructs, site-directed mutagenesis, JAK/STAT inhibitors, dominant-negative studies Clinical and Experimental Immunology High 16045735
2005 CCL26 expressed on the surface of IL-4-stimulated airway epithelial cells is the critical mediator of eosinophil transepithelial migration via CCR3. Cell surface-bound CCL26 (which is predominantly membrane-associated rather than secreted) was partially glycosaminoglycan-dependent but also protein-dependent. Antibody blockade of CCL26 or CCR3 abolished this transepithelial migration. In vitro transepithelial chemotaxis assay, antibody blockade, confocal microscopy (surface-bound protein localization) European Journal of Immunology High 16983721
2005 CCL26 produced by alveolar epithelial cells (A549) downregulates CCR3 receptor expression by 30-40% and inhibits IL-4/IL-13-induced CCL26 secretion in an autocrine/autoregulatory loop; a CCR3-specific antagonist (SB-328437) significantly decreased IL-4-dependent CCL26 synthesis and release. ELISA, CCR3 receptor expression (flow cytometry), cycloheximide/actinomycin D inhibition, CCR3 antagonist treatment, anti-CCR3 pre-treatment American Journal of Physiology. Lung Cellular and Molecular Physiology Medium 15863444
2005 dsRNA (poly(IC)) transfection into airway epithelial cells enhances subsequent IL-4-induced CCL26 production by upregulating IL-4Rα and IL-2Rγ expression, thereby amplifying IL-4-mediated STAT6 phosphorylation; this was reversed by anti-IL-4Rα antibody. ELISA, RT-PCR, Western blot (STAT6 phosphorylation), antibody blockade, cycloheximide/dexamethasone treatment The European Respiratory Journal Medium 16264039
2010 CCL26 is a functional agonist for CX3CR1 (the fractalkine receptor): it induced calcium flux and chemotaxis in L1.2 cells expressing human CX3CR1 (but not mouse CX3CR1) and competed with CX3CL1 for CX3CR1 binding. In human PBMCs, CCL26 attracted CD16+ NK cells, CD45RA+CD27-CD8+ T cells, and CD14lowCD16high monocytes via CX3CR1. IL-4-stimulated HUVECs producing CCL26 efficiently induced adhesion of CX3CR1-expressing cells. Calcium flux assay, chemotaxis assay, radioligand competition binding, intraperitoneal injection model (mouse), flow cytometry, real-time PCR Journal of Immunology High 20974991
2010 CCL26 promotes human lung fibroblast migration but does not stimulate proliferation, collagen synthesis, α-smooth muscle actin expression, or TGF-β1 release, in contrast to CCL24 which stimulates fibroblast proliferation and collagen synthesis but not migration. Thymidine incorporation (proliferation), hydroxyproline incorporation (collagen), Boyden chamber chemotaxis, immunostaining (α-SMA), ELISA (TGF-β1) Annals of Allergy, Asthma & Immunology Medium 20143648
2010 IL-4 induces CCL26 mRNA and protein in human monocytes, monocyte-derived macrophages, and U937 cells via STAT6; TNF-α and IL-1β synergize with IL-4 at a step downstream of STAT6 activation. IFN-γ pre-treatment suppresses IL-4-mediated STAT6 phosphorylation and reduces total STAT6 protein, thereby inhibiting CCL26 expression. RT-PCR, ELISA, Western blot (STAT6 phosphorylation), cytokine stimulation combinations Immunology Medium 20059579
2011 IL-13-induced CCL26 transcription is regulated epigenetically: CBP (CREB-binding protein), a histone acetyltransferase, promotes basal and IL-13-induced CCL26 promoter activity. IL-13 promotes formation of a CBP–STAT6 complex and histone H3 acetylation at the CCL26 promoter. CBP gene silencing decreases IL-13-induced CCL26 transcription; conversely, histone deacetylase inhibition increases it. A CRE site in the CCL26 promoter is required for IL-13-induced activity. Promoter-reporter assays, ChIP (histone acetylation, CBP, STAT6 occupancy), siRNA knockdown, HDAC inhibitor treatment The Journal of Biological Chemistry High 21325281
2012 IL-4 regulates CCL26 in keratinocytes via JAK1/JAK2–STAT6; serial 5′ promoter deletion and mutagenesis identified the proximal STAT6 site as the key response element; IL-4 activates STAT6 (not STAT3) and induces its nuclear translocation; JAK inhibitors suppress CCL26 upregulation in a dose-dependent manner. RT-PCR, ELISA, promoter-reporter assay, 5′ deletion series, site-directed mutagenesis, dominant-negative STAT studies, JAK inhibitors, Western blot (STAT3/6 phosphorylation), nuclear translocation assay Molecular Immunology High 22226123
2012 Omeprazole (and lansoprazole) blocks IL-4-stimulated CCL26 promoter activation and secretion in EoE esophageal epithelial cells by preventing nuclear binding of STAT6, RNA polymerase II, and trimethylated H3K4 to the endogenous CCL26 promoter, without affecting STAT6 phosphorylation or nuclear translocation, and without affecting CCL26 mRNA stability. ELISA, RT-PCR, Western blot (STAT6 phosphorylation/translocation), promoter-reporter construct, ChIP (STAT6, RNA Pol II, H3K4me3) PloS One High 23185525
2013 DNA demethylation of a specific CpG site (CpG 2) in the CCL26 promoter, juxtaposed to a CRE site, is associated with elevated basal and IL-13-induced CCL26 expression in allergic tissue-derived epithelial cells; CpG 2 methylation inversely correlates with CCL26 expression. EMSA demonstrated that CREB-binding protein and ATF-2 binding to the CRE site is methylation-dependent. 5-Azacytidine treatment promotes CCL26 production. Bisulfite sequencing, promoter-reporter assay (methylation-free in vitro system), 5-azacytidine treatment, EMSA Journal of Immunology High 24323578
2013 CCL26 binds to CX3CR1 on NK cells and promotes F-actin reorganization and NK cell chemotaxis via a tyrosine kinase-sensitive pathway (genistein-sensitive); a single antigen nasal provocation challenge increases CX3CR1 expression on NK cells in allergic rhinitis patients, augmenting NK cell chemotaxis toward CCL26. Microchemotaxis chambers, flow cytometry, confocal microscopy (F-actin), genistein (tyrosine kinase inhibitor) blockade Clinical and Experimental Allergy Medium 23414540
2013 CCL26 expression in colonic myofibroblasts is induced by IL-4 and IL-13 via STAT6; IFN-γ acts as a negative regulator via STAT1 activation. SOCS1 is also implicated as a regulatory component of the pathway. RT-PCR, ELISA, Western blot (STAT6/STAT1 signaling), cytokine stimulation Clinical and Experimental Immunology Medium 23607908
2013 CCL26 stimulates migration, invasion, and MMP2 activity of extravillous trophoblast-derived HTR8/SVneo cells, and increases cell adhesion to collagen IV and fibronectin; no effect on TIMP2 activity. xCELLigence real-time cell migration, wound-healing assay, Matrigel invasion assay, zymography (MMP2), reverse zymography (TIMP2), adhesion assay Human Reproduction Medium 23477905
2015 CCL26 exhibits direct bactericidal activity against airway pathogens (S. pneumoniae, S. aureus, H. influenzae, P. aeruginosa) via membrane disruption; the cationic/amphipathic COOH-terminal region is responsible for bactericidal activity. Mast cell chymase and tryptase cleave CCL26 to generate distinct fragments: the COOH-terminal fragment retains antibacterial activity, the NH2-terminal fragment has potent LPS-neutralizing activity, and neither fragment activates CCR3. Viable count assay, electron microscopy, bacterial membrane permeabilization assay, protease cleavage (chymase, tryptase), LPS neutralization assay, CCR3 activation assay Allergy High 25377782
2015 JAK-STAT6 pathway inhibitors (AS1517499, leflunomide, ruxolitinib) block Th2 cytokine-stimulated CCL26 expression in esophageal fibroblasts and epithelial cells by inhibiting STAT6 phosphorylation and nuclear translocation. Omeprazole does not inhibit cytokine-stimulated CCL26 expression in esophageal fibroblasts (negative result for omeprazole in fibroblasts vs. positive in epithelial cells). ELISA, Western blot (STAT6 phosphorylation/translocation), JAK-STAT inhibitor treatment, nuclear translocation assay PloS One Medium 27310888
2016 IL-13-induced CCL26 expression in airway epithelial cells is mediated through a nongastric H,K-ATPase (encoded by ATP12A): knockdown of ATP12A significantly attenuates IL-13-induced CCL26 expression. PPIs block IL-13-enhanced H+/K+ exchange (detected by intracellular pH imaging) and CCL26 expression, and also accelerate IL-13-induced CCL26 mRNA decay. ELISA, Western blot, RT-PCR, intracellular pH imaging, siRNA knockdown (ATP12A), H,K-ATPase inhibitor (SCH-28080), extracellular K+ manipulation The Journal of Allergy and Clinical Immunology High 27717558
2018 CISH (a SOCS family member) is a negative regulator of IL-13-induced CCL26 production in human lung fibroblasts; CISH is itself induced by IL-13 via STAT6 phosphorylation. Loss-of-function (siRNA) increases CCL26, and gain-of-function (overexpression) decreases IL-13-induced CCL26 expression. cDNA microarray, quantitative RT-PCR, ELISA, Western blot, siRNA knockdown, vector overexpression Allergology International Medium 30197185
2019 15-Lipoxygenase 1 (15LO1) promotes CCL26 expression in nasal epithelial cells via ERK activation: 15LO1 knockdown (DsiRNA) and enzymatic inhibition decreased IL-13-induced ERK phosphorylation and CCL26 expression; ERK inhibition alone also decreased IL-13-induced CCL26. Quantitative RT-PCR, Western blot (15LO1, CCL26, phospho-ERK), ELISA, ALOX15 DsiRNA knockdown, specific 15LO1 inhibitor, ERK inhibitors, air-liquid interface culture The Journal of Allergy and Clinical Immunology High 31301373
2021 IL-4-stimulated CCL26 secretion in EoE esophageal squamous cells requires a nongastric H,K-ATPase (ngH+,K+ATPase; ATP12A) and intracellular calcium: IL-4 increases calcium via endoplasmic reticulum release (blocked by 2-APB) and L-type calcium channel entry (blocked by verapamil and diltiazem); chelation of intracellular calcium (EGTA-AM) blocks CCL26 secretion. Omeprazole and SCH-28080 also block IL-4-induced CCL26 secretion. Combined omeprazole + verapamil suppressed CCL26 more than either alone. ELISA, qRT-PCR, Western blot, Fluo-4 fluorescence (intracellular calcium), pharmacological inhibitors (omeprazole, SCH-28080, EGTA-AM, 2-APB, verapamil, diltiazem), primary EoE cells, RNA-seq validation Gastroenterology High 33581123
2023 Airway epithelial cell-derived CCL26 activates CX3CR1+ alveolar macrophages via CCL26–CX3CR1 receptor-ligand interaction, inducing these macrophages to secrete C1q which facilitates eosinophil clearance, thereby resolving allergic lung eosinophilia. Conditional knockout of CCL26 in airway epithelial cells or depletion of CX3CR1 macrophages both delayed resolution with prolonged tissue eosinophilia. Mass cytometry, single-cell RNA sequencing, conditional CCL26 knockout mice, CX3CR1 macrophage depletion, biophysical binding assays, allergen bronchoprovocation (human), immunological assays American Journal of Respiratory and Critical Care Medicine High 36790376
2011 CCL26 promoter activation by IL-13 requires the CRE site; the STAT6 pathway drives CCL26 expression but a CBP–STAT6 complex formation and subsequent histone H3 acetylation at the CCL26 promoter locus are mechanistically required for full transcriptional output. ChIP (CBP, STAT6, acetylated H3), promoter-reporter, CBP siRNA, HDAC inhibitor The Journal of Biological Chemistry High 21325281
2011 STAT6 phosphorylation inhibitors directly bind STAT6 and prevent its active dimer formation, blocking CCL26 secretion by bronchial epithelial cells stimulated with IL-4. Small molecule STAT6 inhibitor (compound R-84), ELISA (CCL26 secretion), STAT6 phosphorylation assay Bioorganic & Medicinal Chemistry Medium 22217933
2012 LTD4 potentiates IL-13-induced CCL26 release by airway epithelial cells via CysLT1 receptor upregulation; IL-13 first upregulates CysLT1 expression, increasing cellular responsiveness to LTD4 which then amplifies CCL26 secretion. LTD4 alone weakly induced CCL26; it had no effect on IL-4-stimulated cells. ELISA, RT-PCR, flow cytometry (CysLT1 expression), time-course stimulation PloS One Medium 22952702
2017 PRL-3 (phosphatase of regenerating liver-3) upregulates CCL26 expression in colorectal cancer cells; CCL26 then binds CCR3 on tumor-associated macrophages (TAMs), mobilizing intracellular Ca2+ in TAMs and increasing IL-6 and IL-8 expression, which enhances colorectal cancer cell invasiveness. Gene ontology analysis, IHC (PRL-3, CCL26, CCR3), CCR3-CCL26 binding/co-culture assay, intracellular Ca2+ mobilization assay, Matrigel invasion assay, in vivo mouse injection model Molecular Cancer Therapeutics Medium 29051319
2021 CCL26 promotes pancreatic cancer cell invasion via activation of the PI3K/AKT/mTOR pathway: recombinant CCL26 treatment of PDAC cell lines increased phosphorylation of PI3K, AKT, and mTOR, and enhanced invasiveness in Matrigel transwell assays. Transwell migration/invasion assay, Western blot (p-PI3K, p-AKT, p-mTOR), RT-qPCR, IHC, recombinant CCL26 treatment Acta Biochimica et Biophysica Sinica Medium 33764366

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2012 Omeprazole blocks eotaxin-3 expression by oesophageal squamous cells from patients with eosinophilic oesophagitis and GORD. Gut 277 22580413
2009 Immobilized-metal affinity chromatography (IMAC): a review. Methods in enzymology 245 19892187
2012 Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PloS one 206 23185525
2011 Clinical and demographic predictors of outcomes in recent onset dilated cardiomyopathy: results of the IMAC (Intervention in Myocarditis and Acute Cardiomyopathy)-2 study. Journal of the American College of Cardiology 204 21884947
1999 Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3. The Journal of biological chemistry 171 10488147
2005 Specificity of immobilized metal affinity-based IMAC/C18 tip enrichment of phosphopeptides for protein phosphorylation analysis. Analytical chemistry 163 16097752
2006 Phosphoproteomic analysis of rat liver by high capacity IMAC and LC-MS/MS. Journal of proteome research 128 16396499
2008 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. Journal of proteome research 126 18220336
2007 Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS. Molecular & cellular proteomics : MCP 124 17208939
2014 Proton pump inhibitor-responsive oesophageal eosinophilia correlates with downregulation of eotaxin-3 and Th2 cytokines overexpression. Alimentary pharmacology & therapeutics 122 25112708
2019 PhoX: An IMAC-Enrichable Cross-Linking Reagent. ACS central science 110 31572778
2003 Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells. Cellular immunology 107 14698143
2007 Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition 104 17592361
2007 Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Human pathology 102 17900656
2003 Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes. Blood 95 12689946
2010 Eotaxin-3/CC chemokine ligand 26 is a functional ligand for CX3CR1. Journal of immunology (Baltimore, Md. : 1950) 92 20974991
2003 Significant elevation of serum levels of eotaxin-3/CCL26, but not of eotaxin-2/CCL24, in patients with atopic dermatitis: serum eotaxin-3/CCL26 levels reflect the disease activity of atopic dermatitis. Clinical and experimental immunology 91 14616792
2007 A novel method to quantify sphingosine 1-phosphate by immobilized metal affinity chromatography (IMAC). Prostaglandins & other lipid mediators 89 17991617
2008 Eotaxin-3 is involved in Churg-Strauss syndrome--a serum marker closely correlating with disease activity. Rheumatology (Oxford, England) 85 18397958
2010 Optimized IMAC-IMAC protocol for phosphopeptide recovery from complex biological samples. Journal of proteome research 84 20450229
2012 Epithelial eotaxin-2 and eotaxin-3 expression: relation to asthma severity, luminal eosinophilia and age at onset. Thorax 83 23015684
2015 Correlation between CCL26 production by human bronchial epithelial cells and airway eosinophils: Involvement in patients with severe eosinophilic asthma. The Journal of allergy and clinical immunology 82 25936567
2012 Cancer-associated fibroblasts up-regulate CCL2, CCL26, IL6 and LOXL2 genes related to promotion of cancer progression in hepatocellular carcinoma cells. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 81 22739041
2005 Eotaxin-2 and eotaxin-3 expression is associated with persistent eosinophilic bronchial inflammation in patients with asthma after allergen challenge. The Journal of allergy and clinical immunology 81 15805998
2005 Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells. Clinical and experimental immunology 81 16045735
2011 Enhancing the identification of phosphopeptides from putative basophilic kinase substrates using Ti (IV) based IMAC enrichment. Molecular & cellular proteomics : MCP 77 21715320
2004 Eotaxin-3/CCL26 is a natural antagonist for CC chemokine receptors 1 and 5. A human chemokine with a regulatory role. The Journal of biological chemistry 76 15039444
2012 Diagnostic utility of major basic protein, eotaxin-3, and leukotriene enzyme staining in eosinophilic esophagitis. The American journal of gastroenterology 73 22777338
2006 Eosinophilic nasal polyps are a rich source of eotaxin, eotaxin-2 and eotaxin-3. Rhinology 72 16792175
2016 Proton pump inhibitors decrease eotaxin-3/CCL26 expression in patients with chronic rhinosinusitis with nasal polyps: Possible role of the nongastric H,K-ATPase. The Journal of allergy and clinical immunology 70 27717558
2018 Defeating Major Contaminants in Fe3+- Immobilized Metal Ion Affinity Chromatography (IMAC) Phosphopeptide Enrichment. Molecular & cellular proteomics : MCP 68 29449344
2011 Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study. Rheumatology (Oxford, England) 67 21266446
2012 Separation and identification of zinc-chelating peptides from sesame protein hydrolysate using IMAC-Zn²⁺ and LC-MS/MS. Food chemistry 66 23107753
2016 JAK-STAT6 Pathway Inhibitors Block Eotaxin-3 Secretion by Epithelial Cells and Fibroblasts from Esophageal Eosinophilia Patients: Promising Agents to Improve Inflammation and Prevent Fibrosis in EoE. PloS one 65 27310888
2012 IL-4 regulates chemokine CCL26 in keratinocytes through the Jak1, 2/Stat6 signal transduction pathway: Implication for atopic dermatitis. Molecular immunology 65 22226123
2022 A Membrane-Permeable and Immobilized Metal Affinity Chromatography (IMAC) Enrichable Cross-Linking Reagent to Advance In Vivo Cross-Linking Mass Spectrometry. Angewandte Chemie (International ed. in English) 63 34927332
2019 15-Lipoxygenase 1 in nasal polyps promotes CCL26/eotaxin 3 expression through extracellular signal-regulated kinase activation. The Journal of allergy and clinical immunology 62 31301373
2005 Cell chromatography: separation of different microbial cells using IMAC supermacroporous monolithic columns. Biotechnology progress 62 15801813
2017 CCL26 Participates in the PRL-3-Induced Promotion of Colorectal Cancer Invasion by Stimulating Tumor-Associated Macrophage Infiltration. Molecular cancer therapeutics 60 29051319
2015 Complementary IMAC enrichment methods for HLA-associated phosphopeptide identification by mass spectrometry. Nature protocols 60 26247297
2002 Regulation of human eotaxin-3/CCL26 expression: modulation by cytokines and glucocorticoids. Cytokine 59 12061839
2013 Comparison of the nasal release of IL-4, IL-10, IL-17, CCL13/MCP-4, and CCL26/eotaxin-3 in allergic rhinitis during season and after allergen challenge. American journal of rhinology & allergy 57 23883806
2010 Eotaxin-2/CCL24 and eotaxin-3/CCL26 exert differential profibrogenic effects on human lung fibroblasts. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 51 20143648
2001 Detection of mRNA for eotaxin-2 and eotaxin-3 in human dermal fibroblasts and their distinct activation profile on human eosinophils. The Journal of investigative dermatology 51 11286614
2009 Enrichment and characterization of phosphopeptides by immobilized metal affinity chromatography (IMAC) and mass spectrometry. Methods in molecular biology (Clifton, N.J.) 49 19241004
2011 Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid. Clinical and experimental immunology 46 21985360
2011 PGD2 induces eotaxin-3 via PPARγ from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis. The Journal of allergy and clinical immunology 45 22206772
2005 Cytokine-stimulated human lung alveolar epithelial cells release eotaxin-2 (CCL24) and eotaxin-3 (CCL26). Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research 44 15695929
2014 Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia. PloS one 43 24988451
2013 Purification and characterization of calcium-binding soybean protein hydrolysates by Ca2+/Fe3+ immobilized metal affinity chromatography (IMAC). Food chemistry 43 23870872
2006 Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC. Proteomics 43 16470654
2010 Analysis of eotaxin 1/CCL11, eotaxin 2/CCL24 and eotaxin 3/CCL26 expression in lesional and non-lesional skin of patients with atopic dermatitis. Cytokine 41 20236835
2020 Zirconium(IV)-IMAC Revisited: Improved Performance and Phosphoproteome Coverage by Magnetic Microparticles for Phosphopeptide Affinity Enrichment. Journal of proteome research 40 33226818
2011 Epigenetic regulation of the IL-13-induced human eotaxin-3 gene by CREB-binding protein-mediated histone 3 acetylation. The Journal of biological chemistry 40 21325281
2009 Identification and characteristics of iron-chelating peptides from soybean protein hydrolysates using IMAC-Fe3+. Journal of agricultural and food chemistry 39 19445472
2006 Phosphopeptide detection using automated online IMAC-capillary LC-ESI-MS/MS. Proteomics 39 16342239
2013 Combination of multistep IMAC enrichment with high-pH reverse phase separation for in-depth phosphoproteomic profiling. Journal of proteome research 38 23927012
2011 Quantitative phosphoproteomics studies using stable isotope dimethyl labeling coupled with IMAC-HILIC-nanoLC-MS/MS for estrogen-induced transcriptional regulation. Journal of proteome research 37 21210654
2006 Membrane-bound eotaxin-3 mediates eosinophil transepithelial migration in IL-4-stimulated epithelial cells. European journal of immunology 36 16983721
2002 Regulatory effects of eotaxin, eotaxin-2, and eotaxin-3 on eosinophil degranulation and superoxide anion generation. Experimental biology and medicine (Maywood, N.J.) 36 12192108
2013 Novel cooperation between CX3CL1 and CCL26 inducing NK cell chemotaxis via CX3CR1: a possible mechanism for NK cell infiltration of the allergic nasal tissue. Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology 35 23414540
2010 Insulin like growth factor-1-induced phosphorylation and altered distribution of tuberous sclerosis complex (TSC)1/TSC2 in C2C12 myotubes. The FEBS journal 35 20412061
2001 NMR solution structure and backbone dynamics of the CC chemokine eotaxin-3. Biochemistry 35 11425309
2006 Regulatory mechanisms of galectin-9 and eotaxin-3 synthesis in epidermal keratinocytes: possible involvement of galectin-9 in dermal eosinophilia of Th1-polarized skin inflammation. Allergy 32 17073866
2005 Autoregulation of CCL26 synthesis and secretion in A549 cells: a possible mechanism by which alveolar epithelial cells modulate airway inflammation. American journal of physiology. Lung cellular and molecular physiology 32 15863444
2021 In Esophageal Squamous Cells From Eosinophilic Esophagitis Patients, Th2 Cytokines Increase Eotaxin-3 Secretion Through Effects on Intracellular Calcium and a Non-Gastric Proton Pump. Gastroenterology 31 33581123
2014 Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation. International forum of allergy & rhinology 31 24989688
2013 Control of extravillous trophoblast function by the eotaxins CCL11, CCL24 and CCL26. Human reproduction (Oxford, England) 30 23477905
2007 Quantitative comparison of IMAC and TiO2 surfaces used in the study of regulated, dynamic protein phosphorylation. Journal of the American Society for Mass Spectrometry 30 17870612
2004 TGF-beta differentially regulates TH2 cytokine-induced eotaxin and eotaxin-3 release by human airway smooth muscle cells. The Journal of allergy and clinical immunology 30 15480317
2004 Upregulation of interleukin-4 receptor by interferon-gamma: enhanced interleukin-4-induced eotaxin-3 production in airway epithelium. American journal of respiratory cell and molecular biology 29 15231490
2018 Multiple Critical Periods for Rapamycin Treatment to Correct Structural Defects in Tsc-1-Suppressed Brain. Frontiers in molecular neuroscience 27 30467464
2016 Epitope imprinting enhanced IMAC (EI-IMAC) for highly selective purification of His-tagged protein. Journal of materials chemistry. B 27 32263073
2015 Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases. Allergy 27 25377782
2006 Differential regulation of eotaxin-1/CCL11 and eotaxin-3/CCL26 production by the TNF-alpha and IL-4 stimulated human lung fibroblast. Biological & pharmaceutical bulletin 26 16755001
2004 Regulatory mechanisms of Th2 cytokine-induced eotaxin-3 production in bronchial epithelial cells: possible role of interleukin 4 receptor and nuclear factor-kappaB. Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 26 15521376
2009 Chitin stimulates expression of acidic mammalian chitinase and eotaxin-3 by human sinonasal epithelial cells in vitro. American journal of rhinology & allergy 25 19379605
2010 Regulation of eotaxin-3/CCL26 expression in human monocytic cells. Immunology 24 20059579
2020 Thermal Bioprinting Causes Ample Alterations of Expression of LUCAT1, IL6, CCL26, and NRN1L Genes and Massive Phosphorylation of Critical Oncogenic Drug Resistance Pathways in Breast Cancer Cells. Frontiers in bioengineering and biotechnology 23 32154227
2013 Regulation of eotaxin-3/CC chemokine ligand 26 expression by T helper type 2 cytokines in human colonic myofibroblasts. Clinical and experimental immunology 23 23607908
2019 CCL26 and CCR3 are associated with the acute inflammatory response in the CNS in experimental autoimmune encephalomyelitis. Journal of neuroimmunology 22 31151084
2014 Eotaxin-3 activates the Smad pathway through the transforming growth factor beta 1 in chronic subdural hematoma outer membranes. Journal of neurotrauma 22 24684589
2014 Puerarin attenuates airway inflammation by regulation of eotaxin-3. Immunology letters 22 25530546
2004 The suggestive association of eotaxin-2 and eotaxin-3 gene polymorphisms in Korean population with allergic rhinitis. Immunogenetics 22 15580493
2017 Separation and Characterization of Angiotensin I Converting Enzyme (ACE) Inhibitory Peptides from Saurida elongata Proteins Hydrolysate by IMAC-Ni2. Marine drugs 20 28212269
2013 Demethylation of the human eotaxin-3 gene promoter leads to the elevated expression of eotaxin-3. Journal of immunology (Baltimore, Md. : 1950) 20 24323578
2020 Utility of major basic protein, eotaxin-3, and mast cell tryptase staining for prediction of response to topical steroid treatment in eosinophilic esophagitis: analysis of a randomized, double-blind, double dummy clinical trial. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 19 32193541
2018 CISH is a negative regulator of IL-13-induced CCL26 production in lung fibroblasts. Allergology international : official journal of the Japanese Society of Allergology 19 30197185
2014 The impact of immobilized metal affinity chromatography (IMAC) resins on DNA aptamer selection. Analytical and bioanalytical chemistry 19 24924211
2011 STAT6 phosphorylation inhibitors block eotaxin-3 secretion in bronchial epithelial cells. Bioorganic & medicinal chemistry 19 22217933
2016 Circulating Levels of the Adipokines Monocyte Chemotactic Protein-4 (MCP-4), Macrophage Inflammatory Protein-1β (MIP-1β), and Eotaxin-3 in Severe Obesity and Following Bariatric Surgery. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 27300476
2013 IMAC fractionation in combination with LC-MS reveals H2B and NIF-1 peptides as potential bladder cancer biomarkers. Journal of proteome research 18 23924207
2023 CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26. American journal of respiratory and critical care medicine 17 36790376
2021 CCL26 is upregulated by nab-paclitaxel in pancreatic cancer-associated fibroblasts and promotes PDAC invasiveness through activation of the PI3K/AKT/mTOR pathway. Acta biochimica et biophysica Sinica 17 33764366
2005 Chronic aeroallergen during infancy enhances eotaxin-3 expression in airway epithelium and nerves. American journal of respiratory cell and molecular biology 17 15834047
2005 dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells. The European respiratory journal 17 16264039
2016 PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells. PloS one 16 27010397
2016 Procyanidin A2 Modulates IL-4-Induced CCL26 Production in Human Alveolar Epithelial Cells. International journal of molecular sciences 16 27845745
2012 Leukotriene D4 and interleukin-13 cooperate to increase the release of eotaxin-3 by airway epithelial cells. PloS one 16 22952702
1996 Fractionation of perforin and granzymes by immobilized metal affinity chromatography (IMAC). Journal of immunological methods 16 8642196

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