Affinage

CCL26

C-C motif chemokine 26 · UniProt Q9Y258

Length
94 aa
Mass
10.6 kDa
Annotated
2026-04-28
100 papers in source corpus 29 papers cited in narrative 29 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL26 (eotaxin-3) is a CC chemokine that functions as a selective CCR3 agonist driving eosinophil chemotaxis, degranulation, and transepithelial migration, while simultaneously acting as a natural antagonist at CCR1, CCR2, and CCR5 on monocytes (PMID:10415065, PMID:12689946, PMID:15039444). Its expression is induced by IL-4 and IL-13 through a JAK1/JAK2–STAT6 axis centered on a proximal STAT6 promoter element, with additional regulation by MEK/ERK, p38 MAPK, nongastric H⁺,K⁺-ATPase/intracellular calcium signaling, 15LO1–ERK signaling, and negative feedback via CISH (PMID:22226123, PMID:27717558, PMID:31301373, PMID:30197185). Beyond its chemotactic role, CCL26 exhibits direct bactericidal activity through its cationic C-terminal domain—an activity modulated by mast cell chymase and tryptase—and signals through CX3CR1 on alveolar macrophages to promote C1q-mediated eosinophil clearance and resolution of allergic airway inflammation (PMID:25377782, PMID:36790376). CCL26 also acts on non-immune cells, promoting trophoblast migration and MMP2 activation, fibroblast chemotaxis, and tumor-associated macrophage recruitment via CCR3 in colorectal cancer (PMID:23477905, PMID:20143648, PMID:29051319).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    Identification of CCL26 as a selective CCR3 ligand established that eosinophil recruitment uses a dedicated chemokine–receptor axis distinct from other CC chemokine pathways.

    Evidence Differential display cloning, recombinant protein calcium flux assay, chemotaxis, competitive radioligand binding on CCR3-transfected cells, and in vivo eosinophil accumulation in cynomolgus monkeys

    PMID:10415065

    Open questions at the time
    • No crystal structure of the CCL26–CCR3 complex
    • In vivo specificity of CCR3-dependence not confirmed by receptor knockout
  2. 2001 High

    The NMR solution structure revealed a monomeric chemokine fold with flexible N-terminal and N-loop regions implicated in CCR3 activation, providing a structural basis for receptor engagement and specificity.

    Evidence NMR spectroscopy with 15N relaxation dynamics and model-free analysis

    PMID:11425309

    Open questions at the time
    • No co-structure with CCR3
    • Functional validation of specific residues by mutagenesis not reported in this study
  3. 2001 High

    Demonstration that surface-associated CCL26 on IL-4-stimulated endothelium drives shear-dependent eosinophil transmigration via CCR3/Gi signaling established a haptotactic mechanism for eosinophil recruitment across vascular barriers.

    Evidence RT-PCR, Western blot, anti-eotaxin-3 and anti-CCR3 antibody blocking, pertussis toxin, laminar flow transmigration assay on HUVECs

    PMID:11748272

    Open questions at the time
    • Identity of surface-anchoring proteins/GAGs not fully resolved
    • In vivo relevance of surface-bound vs. soluble CCL26 not tested
  4. 2002 Medium

    Characterization of IL-4/IL-13 as the primary inducers (with TNF-α synergy and dexamethasone suppression) in fibroblasts and epithelial cells defined the Th2 cytokine dependence of CCL26 transcription.

    Evidence Northern hybridization with dose-response and time-course cytokine stimulation in dermal fibroblasts and lung epithelial cells

    PMID:12061839

    Open questions at the time
    • Signaling intermediates not mapped in this study
    • Promoter elements not identified
  5. 2003 High

    Discovery that CCL26 acts as a natural antagonist at CCR2 (and later CCR1/CCR5) while being an agonist at CCR3 revealed an unusual dual-function chemokine that simultaneously recruits eosinophils and repels monocytes.

    Evidence Chemotaxis/chemorepulsion, Ca²⁺ mobilization, ERK phosphorylation, enzyme release in monocytes and CCR2/CCR1/CCR5-transfected cells with pertussis toxin and receptor antagonists

    PMID:12689946 PMID:15039444

    Open questions at the time
    • Structural basis for agonist vs. antagonist behavior at different receptors not resolved at atomic level
    • In vivo relevance of monocyte chemorepulsion not demonstrated
  6. 2003 Medium

    Mapping CCR3-downstream signaling (ERK1/2, p38 MAPK, PI3K) for CCL26-induced eosinophil degranulation delineated the effector pathways linking receptor engagement to functional eosinophil activation.

    Evidence Eosinophil peroxidase release assay with pharmacological inhibitors in HL-60 eosinophilic cells

    PMID:12784909

    Open questions at the time
    • Performed in HL-60 differentiated line, not primary eosinophils
    • Relative contribution of each pathway not quantified
  7. 2005 High

    Identification of the proximal STAT6 binding site as the key IL-4 response element in the CCL26 promoter, via JAK1/JAK2–STAT6, established the core transcriptional mechanism for Th2-induced CCL26 expression.

    Evidence Promoter deletion, site-directed mutagenesis, dominant-negative STAT constructs, JAK inhibitors in HaCaT keratinocytes; confirmed and extended in 2012 study

    PMID:16045735 PMID:22226123

    Open questions at the time
    • Chromatin accessibility and epigenetic regulation at this locus not characterized beyond H3K4me3 at the time
    • Cell-type-specific enhancers not mapped
  8. 2005 Medium

    The finding that CCL26 autoregulates its own synthesis via CCR3 on epithelial cells revealed a negative feedback loop limiting eosinophil chemoattractant production.

    Evidence ELISA, flow cytometry for CCR3 expression, CCR3 antagonist SB-328437, neutralizing antibody in A549 cells

    PMID:15863444

    Open questions at the time
    • Autocrine loop not confirmed in primary airway epithelium
    • Downstream signaling mediating the negative feedback not identified
  9. 2006 High

    Demonstration that surface-bound CCL26 on airway epithelial cells is the dominant functional pool driving eosinophil transepithelial migration extended the haptotactic mechanism from endothelium to epithelium.

    Evidence In vitro transepithelial migration assay with anti-eotaxin-3 and anti-CCR3 blocking, surface localization studies in IL-4-stimulated epithelial cells

    PMID:16983721

    Open questions at the time
    • Specific surface-binding proteins not identified
    • Relative contributions of GAG-dependent vs. protein-dependent anchoring not fully resolved
  10. 2012 High

    ChIP studies showing omeprazole blocks STAT6, RNA Pol II, and H3K4me3 recruitment to the CCL26 promoter without affecting STAT6 phosphorylation or nuclear translocation revealed a chromatin-level regulatory mechanism for pharmacological suppression of CCL26.

    Evidence ChIP assay, reporter construct, Western blot for STAT6 phosphorylation/translocation in esophageal squamous cells

    PMID:23185525

    Open questions at the time
    • Direct molecular target of omeprazole at the chromatin level not identified
    • Whether this mechanism operates in vivo in eosinophilic esophagitis tissue not confirmed
  11. 2013 Medium

    CCL26 was found to signal through CX3CR1 on NK cells, expanding its receptor repertoire beyond CCR3 and its antagonist targets.

    Evidence Microchemotaxis chamber, flow cytometry for CX3CR1, confocal microscopy, genistein inhibition on human NK cells

    PMID:23414540

    Open questions at the time
    • Direct binding affinity to CX3CR1 not measured
    • Relative physiological importance of CX3CR1 vs. CCR3 signaling unknown
  12. 2015 High

    Discovery of direct bactericidal activity concentrated in the C-terminal α-helix, with mast cell protease cleavage generating functionally distinct N-terminal (LPS-neutralizing) and C-terminal (bactericidal) fragments, established CCL26 as a bifunctional innate immune effector.

    Evidence Viable count assay, electron microscopy, membrane permeabilization, mass spectrometry of chymase/tryptase cleavage products, LPS neutralization assay

    PMID:25377782

    Open questions at the time
    • In vivo antimicrobial role not demonstrated
    • Whether protease cleavage occurs at mucosal surfaces in allergic tissue not shown
  13. 2016 High

    Identification of nongastric H⁺,K⁺-ATPase (ATP12A) as a mediator of IL-13-induced CCL26 expression linked ion transport and intracellular pH to Th2 chemokine regulation.

    Evidence siRNA knockdown of ATP12A, intracellular pH imaging, proton pump inhibitor treatment in sinonasal epithelial cells

    PMID:27717558

    Open questions at the time
    • How intracellular pH changes feed into STAT6 or ERK signaling not resolved
    • Generalizability beyond sinonasal epithelium not established at that time
  14. 2018 Medium

    CISH, induced by IL-13 via STAT6, was identified as a negative-feedback regulator of CCL26 production, connecting SOCS-family signaling to eosinophil chemoattractant control.

    Evidence siRNA knockdown and overexpression of CISH, cDNA microarray, ELISA, Western blot in human lung fibroblasts

    PMID:30197185

    Open questions at the time
    • Direct mechanism by which CISH suppresses CCL26 transcription not defined
    • Not confirmed in epithelial cells or in vivo
  15. 2019 High

    15-lipoxygenase 1 was shown to promote CCL26 expression via ERK activation, integrating lipid mediator signaling into the transcriptional regulation of this chemokine.

    Evidence DsiRNA knockdown, pharmacological 15LO1 inhibition, ERK inhibitors, ELISA, Western blot in nasal epithelial cells

    PMID:31301373

    Open questions at the time
    • Specific 15LO1 metabolite mediating ERK activation not identified
    • Interaction with STAT6 pathway not fully delineated
  16. 2021 High

    IL-4-induced CCL26 secretion was shown to require ER calcium release and L-type calcium channel entry, with pharmacological blockade (verapamil, diltiazem) suppressing CCL26, connecting the ngH⁺,K⁺-ATPase pathway to a defined calcium signaling mechanism.

    Evidence Fluo-4 calcium imaging, pharmacological inhibitors (omeprazole, verapamil, diltiazem, 2-APB, EGTA-AM), ELISA, RNA-seq of patient biopsies in esophageal squamous cells

    PMID:33581123

    Open questions at the time
    • How calcium flux regulates STAT6 promoter occupancy or mRNA stability not defined
    • Whether calcium channel blockers have therapeutic efficacy in eosinophilic esophagitis not proven
  17. 2023 High

    Conditional CCL26 knockout in airway epithelial cells demonstrated that CCL26 activates CX3CR1⁺ alveolar macrophages to secrete C1q, driving eosinophil clearance and resolution of allergic lung inflammation — establishing CCL26 as a pro-resolution mediator, not just a pro-inflammatory chemokine.

    Evidence Conditional CCL26 knockout mice, CX3CR1 macrophage depletion, mass cytometry, single-cell RNA-seq, human allergen bronchoprovocation

    PMID:36790376

    Open questions at the time
    • Molecular mechanism of CX3CR1 signaling leading to C1q secretion not defined
    • Whether this resolution pathway operates in non-pulmonary tissues unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the atomic-resolution structure of CCL26 bound to CCR3 vs. CX3CR1, the structural determinants that switch CCL26 from agonist (CCR3) to antagonist (CCR1/CCR2/CCR5), the in vivo antimicrobial significance of the C-terminal bactericidal domain, and how the calcium/pH and 15LO1–ERK pathways converge with STAT6 at the chromatin level to regulate CCL26 transcription.
  • No co-crystal or cryo-EM structure of CCL26 with any receptor
  • In vivo antimicrobial function not tested
  • Integrated signaling model connecting STAT6, ERK, calcium, and 15LO1 pathways at the promoter not available

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 3 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 5
Partners
CCR1CCR2CCR3CCR5CX3CR1STAT6

Evidence

Reading pass · 29 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 CCL26 (eotaxin-3) was identified as a novel CC chemokine that binds exclusively to CCR3, inducing cytosolic Ca2+ mobilization and in vitro chemotaxis of eosinophils; it inhibited 125I-eotaxin binding to eosinophils and acted on CCR3-transfected cell lines, and induced eosinophil accumulation in vivo in cynomolgus monkeys. Differential display, recombinant protein production, calcium flux assay, chemotaxis assay, competitive radioligand binding, CCR3-transfected cell lines, in vivo injection Journal of immunology High 10415065
2001 NMR solution structure of CCL26 revealed a monomeric protein with an unstructured N-terminus, N-loop, 3(10)-helix turn, three-stranded antiparallel β-sheet, and C-terminal α-helix; backbone dynamics showed large-amplitude motions in the termini and N-loop implicated in CCR3 receptor binding and activation, and a surface groove and β2-β3 turn were identified as important for receptor specificity. NMR spectroscopy, 15N relaxation dynamics (model-free formalism) Biochemistry High 11425309
2001 IL-4-stimulated HUVECs upregulate eotaxin-3 mRNA and protein; eotaxin-3 is both released and expressed on the endothelial cell surface, and surface-associated eotaxin-3 mediates shear-dependent eosinophil transmigration via CCR3 and pertussis-toxin-sensitive Gi protein signaling. RT-PCR, Western blot, anti-eotaxin-3 antibody blocking, anti-CCR3 antibody blocking, pertussis toxin treatment, laminar flow transmigration assay The Journal of experimental medicine High 11748272
2003 CCL26 binds to CCR2 on monocytes and CCR2-transfected cells but, unlike MCP-1/CCL2, does not trigger intracellular calcium mobilization, enzyme release, or ERK phosphorylation; instead it acts as a natural antagonist for CCR2, inhibiting MCP-1-mediated responses, and promotes active repulsion (reverse migration) of monocytes away from an eotaxin-3 gradient via Gi protein-coupled receptors. Chemotaxis/chemorepulsion assay, Ca2+ mobilization assay, ERK phosphorylation assay, enzyme release assay, CCR2 transfected cells, pertussis toxin treatment, CCR2 antagonist treatment Blood High 12689946
2004 CCL26 also binds to CCR1 and CCR5, acting as a natural antagonist on both receptors by inhibiting chemotaxis, intracellular 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. Chemotaxis assay, Ca2+ mobilization assay, actin polymerization assay, radioligand binding with CCR1/CCR5-transfected cells, 3D structural analysis The Journal of biological chemistry High 15039444
2002 IL-4 and IL-13 induce CCL26 mRNA expression in primary dermal fibroblasts and lung epithelial cells in a time- and dose-dependent manner; IL-4 is ~100-fold more potent than IL-13; TNF-α alone does not induce expression but acts synergistically with IL-4/IL-13; dexamethasone pre-treatment diminishes CCL26 induction. Northern hybridization, cytokine stimulation with dose-response and time-course Cytokine Medium 12061839
2005 IL-4 up-regulates CCL26 in keratinocytes (HaCaT cells) through the JAK1/JAK2–STAT6 pathway; serial promoter deletion and mutagenesis identified the proximal STAT6 binding site as the key IL-4 response element; JAK inhibitors suppress CCL26 production in a dose-dependent manner; IL-4 signaling involves the type 2 IL-4 receptor. RT-PCR, ELISA, promoter deletion/mutagenesis, JAK inhibitors, STAT6 dominant-negative studies Clinical and experimental immunology Medium 16045735
2006 In airway epithelial cells, CCL26 production induced by TNF-α plus IL-4 is regulated by MEK/ERK (blocked by PD98059/U0126) and p38 MAPK (blocked by SB203580) pathways; unlike eotaxin-1/CCL11, CCL26 production is less sensitive to NF-κB inhibition by proteasome inhibitors. ELISA, pharmacological inhibitors of MEK, p38, and proteasome in human lung fibroblasts Biological & pharmaceutical bulletin Medium 16755001
2006 In IL-4-stimulated airway epithelial cells, eotaxin-3/CCL26 is predominantly cell surface bound rather than secreted; cell surface association is partially glycosaminoglycan (GAG) dependent but completely protein dependent, and cell surface-bound eotaxin-3 is critical for eosinophil transepithelial migration via CCR3. In vitro transepithelial chemotaxis assay, CCR3 antibody blocking, epithelial cell surface localization studies, anti-eotaxin-3 blocking European journal of immunology High 16983721
2005 In A549 alveolar epithelial cells, CCL26 autoregulates its own synthesis via the CCR3 receptor: exogenous CCL26 (but not CCL24) reduces IL-4/IL-13-induced CCL26 secretion and downregulates CCR3 expression by 30-40%; a CCR3-specific antagonist (SB-328437) blocks IL-4-dependent CCL26 synthesis. ELISA, flow cytometry for CCR3 expression, anti-CCR3 antibody pretreatment, CCR3 antagonist (SB-328437), cycloheximide and actinomycin D experiments American journal of physiology. Lung cellular and molecular physiology Medium 15863444
2004 IFN-γ has biphasic effects on CCL26 production in bronchial epithelial cells: concurrent IFN-γ inhibits IL-13/IL-4-induced eotaxin-3 by downregulating STAT6 activation, while 2-day pre-treatment with IFN-γ enhances CCL26 production by upregulating IL-4Rα and IL-2Rγ (type 1 IL-4R components). ELISA, RT-PCR, Western blot for STAT6 phosphorylation, IL-4Rα protein expression in BEAS-2B cells American journal of respiratory cell and molecular biology Medium 15231490
2010 In human monocytes and macrophages, IL-4 induces CCL26 mRNA and protein via STAT6; TNF-α and IL-1β synergize with IL-4 at a step downstream of STAT6 activation; IFN-γ pre-treatment decreases total STAT6 protein, blocks IL-4-mediated STAT6 phosphorylation, and suppresses CCL26 expression. RT-PCR, ELISA, Western blot for STAT6 phosphorylation in U937 cells, primary monocytes, and monocyte-derived macrophages Immunology Medium 20059579
2012 IL-4 regulates CCL26 in keratinocytes (HaCaT) via JAK1/JAK2–STAT6: IL-4 activates Stat6 (not Stat3) shown by dominant-negative studies, induces Stat6 nuclear translocation and CCL26 promoter activation; serial 5' deletion and mutagenesis identified the proximal Stat6 site as the key response element. Promoter deletion, site-directed mutagenesis, dominant-negative STAT constructs, Western blot, ELISA, RT-PCR Molecular immunology High 22226123
2012 Omeprazole blocks IL-4-stimulated CCL26 expression in esophageal squamous cells by preventing STAT6 binding to the eotaxin-3 promoter; it has no effect on STAT6 phosphorylation or nuclear translocation, but blocks recruitment of STAT6, RNA Pol II, and trimethylated H3K4 to the CCL26 promoter. ELISA, PCR, Western blot for STAT6 phosphorylation/translocation, reporter construct assay, ChIP assay PloS one High 23185525
2011 IL-13-stimulated CCL26 secretion in lung epithelial cells is regulated by atypical PKC (aPKC)–STAT6 signaling; γ-tocotrienol increases expression of PAR4 (endogenous aPKC inhibitor) and enhances aPKC-PAR4 complex formation, thereby blocking IL-13-induced STAT6 phosphorylation/DNA binding and CCL26 generation. ELISA, siRNA knockdown, pharmacological inhibitors, EMSA (STAT6 DNA binding), Western blot, co-immunoprecipitation of aPKC/PAR4 complex The Journal of nutritional biochemistry Medium 21764283
2011 STAT6 phosphorylation inhibitor compound (R)-84 directly binds STAT6 and prevents its active dimer formation, thereby inhibiting IL-4-induced eotaxin-3 secretion in bronchial epithelial BEAS-2B cells. ELISA, STAT6 binding assay, phosphorylation assay in BEAS-2B cells Bioorganic & medicinal chemistry Medium 22217933
2011 PGD2 and its metabolite 15d-PGJ2 induce eotaxin-3/CCL26 production from sebocytes via peroxisome proliferator-activated receptor gamma (PPARγ), providing a mechanistic pathway linking COX metabolites to eosinophil chemoattractant production in eosinophilic pustular folliculitis. Immunostaining, ELISA, receptor identification in sebocyte cultures The Journal of allergy and clinical immunology Medium 22206772
2013 In human colonic myofibroblasts, IL-4 and IL-13 enhance CCL26 expression through STAT6-mediated pathways; SOCS1 also participates in regulating IL-4/IL-13-induced CCL26; IFN-γ acts as a negative regulator via STAT1 activation. RT-PCR, ELISA, Western blot in primary colonic myofibroblasts with cytokine stimulation Clinical and experimental immunology Medium 23607908
2013 CCL26 induces migration and invasion of extravillous trophoblasts (HTR8/SVneo cells) and increases MMP2 activity; it also promotes adhesion to collagen IV and fibronectin without affecting TIMP2 activity. xCELLigence real-time migration assay, wound-healing assay, Matrigel invasion assay, zymography, reverse zymography, adhesion assay Human reproduction Medium 23477905
2013 CCL26 signals through CX3CR1 (in addition to CCR3) on NK cells to induce chemotaxis, cytoskeleton changes, and F-actin reorganization; this signaling is sensitive to genistein (tyrosine kinase inhibitor); allergen challenge increases CX3CR1 expression on NK cells and augments NK cell chemotaxis toward CCL26. Microchemotaxis chamber, flow cytometry, confocal microscopy, pharmacological inhibition with genistein Clinical and experimental allergy Medium 23414540
2015 CCL26 exhibits direct bactericidal activity against airway pathogens (S. pneumoniae, S. aureus, H. influenzae, P. aeruginosa) by membrane disruption; bactericidal activity is concentrated in the cationic/amphipathic C-terminal region. Mast cell chymase and tryptase cleave CCL26 generating an N-terminal fragment with LPS-neutralizing activity and a C-terminal fragment retaining antibacterial activity; neither fragment activates CCR3. Viable count assay, electron microscopy, bacterial membrane permeabilization assay, mass spectrometry characterization of protease cleavage fragments, LPS neutralization assay Allergy High 25377782
2016 IL-13 induces CCL26 expression in sinonasal epithelial cells via activation of a nongastric H+,K+-ATPase (ATP12A); knockdown of ATP12A significantly attenuated IL-13-induced CCL26 expression; PPIs block this pathway and accelerate IL-13-induced CCL26 mRNA decay. ELISA, Western blot, RT-PCR, intracellular pH imaging, extracellular K+ alteration, siRNA knockdown of ATP12A The Journal of allergy and clinical immunology High 27717558
2019 15-lipoxygenase 1 (15LO1) promotes CCL26/eotaxin-3 expression in nasal epithelial cells through ERK activation; 15LO1 knockdown (DsiRNA) or inhibition decreases IL-13-induced ERK phosphorylation and CCL26 expression; ERK inhibition alone similarly reduces CCL26. DsiRNA knockdown, pharmacological 15LO1 inhibition, ERK inhibitors, ELISA, Western blot, quantitative RT-PCR, immunofluorescence colocalization The Journal of allergy and clinical immunology High 31301373
2018 CISH (a SOCS family member) is induced by IL-13 via STAT6 phosphorylation and acts as a negative regulator of IL-13-induced CCL26 production in human lung fibroblasts; loss-of-function (siRNA) increases CCL26, while gain-of-function (overexpression) decreases CCL26. cDNA microarray, quantitative RT-PCR, ELISA, Western blot, siRNA knockdown, vector overexpression Allergology international Medium 30197185
2021 IL-4 stimulates CCL26 secretion in esophageal squamous cells via ngH+,K+ATPase and an intracellular calcium pathway: IL-4 induces calcium release from the ER and entry via L-type calcium channels, and inhibitors of these channels (verapamil, diltiazem) as well as calcium chelation block CCL26 secretion; omeprazole and verapamil together suppress CCL26 secretion more than either alone. ELISA, QPCR, Western blot, Fluo-4 calcium fluorescence imaging, pharmacological inhibitors (omeprazole, SCH28080, EGTA-AM, 2-APB, verapamil, diltiazem), RNA-seq of patient biopsies Gastroenterology High 33581123
2023 Airway epithelial cell-derived CCL26 binds CX3CR1 on CX3CR1+ alveolar macrophages, activating this subset to secrete C1q, which facilitates eosinophil clearance; conditional knockout of CCL26 in airway epithelial cells or depletion of CX3CR1 macrophages delays resolution of allergic lung inflammation and prolongs tissue eosinophilia. Conditional CCL26 knockout mice, CX3CR1 macrophage depletion, mass cytometry, single-cell RNA sequencing, biophysical and immunological analyses, human allergen bronchoprovocation American journal of respiratory and critical care medicine High 36790376
2010 CCL26 (eotaxin-3/CCL26) but not CCL24 promotes migration (chemotaxis) of human lung fibroblasts, while CCL24 but not CCL26 stimulates proliferation and collagen synthesis; neither chemokine induces alpha-smooth muscle actin or TGF-β1 expression, demonstrating differential profibrogenic activities. 3H-thymidine proliferation assay, 3H-hydroxyproline collagen assay, Boyden chamber chemotaxis, immunostaining for alpha-SMA, ELISA for TGF-β1 Annals of allergy, asthma & immunology Medium 20143648
2003 CCR3-mediated CCL26-induced eosinophil degranulation (EPO release) is reduced by specific inhibitors of ERK1/ERK2 (U0126), p38 MAPK (SB203580), and PI3K (LY294002), establishing that all three pathways are downstream of CCR3 activation by CCL26; IL-5 potentiates CCL26-induced degranulation. Eosinophil peroxidase degranulation assay with pharmacological inhibitors in HL-60 eosinophilic cells Immunopharmacology and immunotoxicology Medium 12784909
2017 PRL-3 upregulates CCL26 expression in colorectal cancer cells; CCL26 binds CCR3 on tumor-associated macrophages, triggering intracellular Ca2+ mobilization and increased IL-6 and IL-8 expression in macrophages, which in turn enhances colorectal cancer cell invasiveness in co-culture. PRL-3 overexpression/silencing, recombinant CCL26 treatment, co-culture invasion assay, calcium mobilization assay, Western blot, IHC, in vivo mouse xenograft Molecular cancer therapeutics Medium 29051319

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 275 22580413
2009 Immobilized-metal affinity chromatography (IMAC): a review. Methods in enzymology 244 19892187
1999 A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils. Journal of immunology (Baltimore, Md. : 1950) 218 10415065
2012 Omeprazole blocks STAT6 binding to the eotaxin-3 promoter in eosinophilic esophagitis cells. PloS one 203 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 203 21884947
2005 Specificity of immobilized metal affinity-based IMAC/C18 tip enrichment of phosphopeptides for protein phosphorylation analysis. Analytical chemistry 162 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 108 31572778
2003 Concerted expression of eotaxin-1, eotaxin-2, and eotaxin-3 in human bronchial epithelial cells. Cellular immunology 107 14698143
2007 Increased expression of eotaxin-3 distinguishes between eosinophilic esophagitis and gastroesophageal reflux disease. Human pathology 101 17900656
2007 SELDI-TOF MS whole serum proteomic profiling with IMAC surface does not reliably detect prostate cancer. Clinical chemistry 97 18024530
2003 Eotaxin-3 is a natural antagonist for CCR2 and exerts a repulsive effect on human monocytes. Blood 95 12689946
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 89 14616792
2007 A novel method to quantify sphingosine 1-phosphate by immobilized metal affinity chromatography (IMAC). Prostaglandins & other lipid mediators 88 17991617
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 80 22739041
2005 Interleukin-4 and interleukin-13 enhance CCL26 production in a human keratinocyte cell line, HaCaT cells. Clinical and experimental immunology 78 16045735
2001 Shear-dependent eosinophil transmigration on interleukin 4-stimulated endothelial cells: a role for endothelium-associated eotaxin-3. The Journal of experimental medicine 78 11748272
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 75 15039444
2018 Defeating Major Contaminants in Fe3+- Immobilized Metal Ion Affinity Chromatography (IMAC) Phosphopeptide Enrichment. Molecular & cellular proteomics : MCP 67 29449344
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 67 27717558
2011 Eotaxin-3 in Churg-Strauss syndrome: a clinical and immunogenetic study. Rheumatology (Oxford, England) 66 21266446
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
2012 IL-4 regulates chemokine CCL26 in keratinocytes through the Jak1, 2/Stat6 signal transduction pathway: Implication for atopic dermatitis. Molecular immunology 62 22226123
2005 Cell chromatography: separation of different microbial cells using IMAC supermacroporous monolithic columns. Biotechnology progress 62 15801813
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) 60 34927332
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
2008 Phosphorylation analysis of primary human T lymphocytes using sequential IMAC and titanium oxide enrichment. Journal of proteome research 60 19367720
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 56 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
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 PGD2 induces eotaxin-3 via PPARγ from sebocytes: a possible pathogenesis of eosinophilic pustular folliculitis. The Journal of allergy and clinical immunology 45 22206772
2011 Up-regulation of CCL11 and CCL26 is associated with activated eosinophils in bullous pemphigoid. Clinical and experimental immunology 44 21985360
2006 Quantitation of protein phosphorylation in pregnant rat uteri using stable isotope dimethyl labeling coupled with IMAC. Proteomics 43 16470654
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 43 15695929
2014 Proton pump inhibitors decrease eotaxin-3 expression in the proximal esophagus of children with esophageal eosinophilia. PloS one 42 24988451
2013 Purification and characterization of calcium-binding soybean protein hydrolysates by Ca2+/Fe3+ immobilized metal affinity chromatography (IMAC). Food chemistry 42 23870872
2020 Zirconium(IV)-IMAC Revisited: Improved Performance and Phosphoproteome Coverage by Magnetic Microparticles for Phosphopeptide Affinity Enrichment. Journal of proteome research 39 33226818
2015 Complementary PTM Profiling of Drug Response in Human Gastric Carcinoma by Immunoaffinity and IMAC Methods with Total Proteome Analysis. Proteomes 39 28248267
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 39 20236835
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
2001 NMR solution structure and backbone dynamics of the CC chemokine eotaxin-3. Biochemistry 35 11425309
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 34 23414540
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
1996 Human perforin: rapid enrichment by immobilized metal affinity chromatography (IMAC) for whole cell cytotoxicity assays. Biochemical and biophysical research communications 32 8954081
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 31 15863444
2014 Nasal fluid release of eotaxin-3 and eotaxin-2 in persistent sinonasal eosinophilic inflammation. International forum of allergy & rhinology 30 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
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 29 33581123
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
2011 Development and application of a phosphoproteomic method using electrostatic repulsion-hydrophilic interaction chromatography (ERLIC), IMAC, and LC-MS/MS analysis to study Marek's Disease Virus infection. Journal of proteome research 28 21736374
2011 Vitamin E forms inhibit IL-13/STAT6-induced eotaxin-3 secretion by up-regulation of PAR4, an endogenous inhibitor of atypical PKC in human lung epithelial cells. The Journal of nutritional biochemistry 27 21764283
2018 Multiple Critical Periods for Rapamycin Treatment to Correct Structural Defects in Tsc-1-Suppressed Brain. Frontiers in molecular neuroscience 26 30467464
2016 Epitope imprinting enhanced IMAC (EI-IMAC) for highly selective purification of His-tagged protein. Journal of materials chemistry. B 26 32263073
2015 Eotaxin-3 (CCL26) exerts innate host defense activities that are modulated by mast cell proteases. Allergy 26 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 Fatty acids induce chloride permeation in rat liver mitochondria by activation of the inner membrane anion channel (IMAC). Journal of bioenergetics and biomembranes 26 15337854
2016 Phosphopeptide enrichment: Development of magnetic solid phase extraction method based on polydopamine coating and Ti(4+)-IMAC. Analytica chimica acta 25 26851086
2017 New Ti-IMAC magnetic polymeric nanoparticles for phosphopeptide enrichment from complex real samples. Talanta 24 29136822
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 22 23607908
2009 Evaluation of immobilized metal-ion affinity chromatography (IMAC) as a technique for IgG(1) monoclonal antibodies purification: the effect of chelating ligand and support. Applied biochemistry and biotechnology 22 19701728
2019 CCL26 and CCR3 are associated with the acute inflammatory response in the CNS in experimental autoimmune encephalomyelitis. Journal of neuroimmunology 21 31151084
2014 Puerarin attenuates airway inflammation by regulation of eotaxin-3. Immunology letters 21 25530546
2017 Separation and Characterization of Angiotensin I Converting Enzyme (ACE) Inhibitory Peptides from Saurida elongata Proteins Hydrolysate by IMAC-Ni2. Marine drugs 19 28212269
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
2013 Comparative analysis of salt-responsive phosphoproteins in maize leaves using Ti(4+)--IMAC enrichment and ESI-Q-TOF MS. Electrophoresis 18 23172588
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
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 17 30197185
2005 dsRNA enhances eotaxin-3 production through interleukin-4 receptor upregulation in airway epithelial cells. The European respiratory journal 17 16264039
2023 CX3CR1+ Macrophage Facilitates the Resolution of Allergic Lung Inflammation via Interacting CCL26. American journal of respiratory and critical care medicine 16 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 16 33764366
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
2002 A recombinant envelope protein from Dengue virus purified by IMAC is bioequivalent with its immune-affinity chromatography purified counterpart. Journal of biotechnology 15 11796173
2023 ATP-Coated Dual-Functionalized Titanium(IV) IMAC Material for Simultaneous Enrichment and Separation of Glycopeptides and Phosphopeptides. Journal of proteome research 14 37195130
2019 The proteolytic effect of mast cell tryptase to eotaxin-1/CCL11·eotaxin-2/CCL24 and eotaxin-3/CCL26 produced by conjunctival fibroblasts. Japanese journal of ophthalmology 14 30796548
2013 Purification of a recombinant human growth hormone by an integrated IMAC procedure. Protein expression and purification 14 24275639
2009 Separation of hexahistidine fusion proteins with immobilized metal ion affinity chromatographic (IMAC) sorbents derived from M(N+)-tacn and its derivatives. Biotechnology and bioengineering 14 19350626
2007 Characterization of phosphorylation sites on Tpl2 using IMAC enrichment and a linear ion trap mass spectrometer. Journal of proteome research 14 17472361
2003 Inhibition of CCL11, CCL24, and CCL26-induced degranulation in HL-60 eosinophilic cells by specific inhibitors of MEK1/MEK2, p38 MAP kinase, and PI 3-kinase. Immunopharmacology and immunotoxicology 14 12784909
2024 TIMAHAC: Streamlined Tandem IMAC-HILIC Workflow for Simultaneous and High-Throughput Plant Phosphoproteomics and N-glycoproteomics. Molecular & cellular proteomics : MCP 13 38608839
2016 The Correlation of Serums CCL11, CCL17, CCL26, and CCL27 and Disease Severity in Patients with Urticaria. Disease markers 13 27057079