Affinage

CCL7

C-C motif chemokine 7 · UniProt P80098

Length
99 aa
Mass
11.2 kDa
Annotated
2026-06-09
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CCL7 (MCP-3) is a secreted CC chemokine that orchestrates leukocyte trafficking during innate and adaptive immune responses by engaging multiple CC chemokine receptors (PMID:8318676, PMID:7589134, PMID:8642349). Originally cloned as a monocyte chemoattractant (PMID:8318676), it binds CCR1 (PMID:7545673), CCR2 (PMID:8662823), and CCR5 (PMID:10477718) with high affinity, and its broad receptor promiscuity—encompassing monocytes, T lymphocytes, eosinophils, and neutrophils—rests on a monomeric architecture bearing GAG-binding epitopes distributed across its surface, allowing high-affinity heparan sulfate binding without oligomerization, distinct from CCL2 (PMID:24727473). Its N-terminus is dispensable for receptor binding but essential for receptor activation, such that N-terminally truncated CCL7 becomes a multi-receptor antagonist (PMID:8631850); at CCR5 the intact chemokine itself behaves as a natural antagonist, binding without triggering signaling or internalization (PMID:10477718). In vivo, epithelial- and endothelial-derived CCL7 is a non-redundant driver of eosinophil and neutrophil recruitment in allergic, oxidative, and infectious airway inflammation (PMID:9144514, PMID:11777981, PMID:12107110, PMID:23972264), while contributing additively with CCL2 to CCR2-dependent inflammatory monocyte egress and Th2 restraint during fungal and bacterial infection (PMID:18453605, PMID:19587014), and acting downstream of TLR9 in antifungal immunity (PMID:22422883). Beyond chemotaxis, CCL7 can negatively regulate neutrophilic inflammation (PMID:30671055) and recruits cDC1 to promote antitumor T cell responses (PMID:33257678). In cancer, CCL7 promotes invasion and metastasis through CCR3-RhoA-MMP-9-dependent invadopodia maturation (PMID:32217106), CCR1-driven transcriptional feedback and acetylation cascades (PMID:32616889, PMID:35283273), and CCR2-JAK/STAT3 signaling that breaks micrometastatic dormancy (PMID:33986252). CCL7 also drives macrophage M1 polarization via CCR1/JAK2/STAT1 (PMID:34189838) and via a CCR1-KAT2A-STAT1 succinylation axis linking it to glycolytic reprogramming in lung injury (PMID:40755420), and impairs endothelial function through CCR3 by suppressing AKT-eNOS signaling (PMID:39231238). Its expression is induced by inflammatory cytokines through NFκB and p38/JNK MAPK pathways (PMID:19577550, PMID:18981157) and by redox-sensitive BRG1-AP-1 chromatin remodeling (PMID:34454163), and is post-transcriptionally controlled by let-7d (PMID:25193015).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1993 High

    Establishing CCL7's molecular identity and core activity answered whether it was a distinct chemoattractant, defining it as a CC chemokine that recruits monocytes and is regulated by inflammatory stimuli.

    Evidence cDNA cloning, recombinant expression, chemotaxis and glycosylation analysis, mRNA regulation studies in U937/PBMC

    PMID:8318676

    Open questions at the time
    • Receptors mediating monocyte chemotaxis not yet identified
    • Neutrophil activity initially absent, later found context-dependent
  2. 1994 Medium

    Identifying the murine orthologue (MARC/FIC) enabled in vivo genetic and infection studies of CCL7 function.

    Evidence cDNA library screening from LPS-stimulated WEHI-3 macrophages with human MCP-3 probe and sequencing

    PMID:8002978

    Open questions at the time
    • Functional conservation with human CCL7 not directly tested at this stage
  3. 1995 High

    Defining the receptor repertoire answered how a single chemokine recruits diverse leukocytes, showing CCL7 binds CCR1 and shares receptor sites with MIP-1α/RANTES/MCP-1 while engaging unique sites.

    Evidence CCR1 transfection with radioligand binding and migration assays; primary monocyte/neutrophil binding and cross-desensitization

    PMID:7545673 PMID:7589134

    Open questions at the time
    • Full receptor set not enumerated
    • Structural basis of promiscuity not yet defined
  4. 1996 High

    Receptor mapping and structure-activity dissection established CCR2 as a murine receptor and showed the N-terminus controls activation versus binding, yielding a multi-receptor antagonist.

    Evidence mCCR2 cloning and radioligand competition; MCP-3(10-76) truncation with binding, chemotaxis and enzyme release assays; leukocyte cross-competition

    PMID:8631850 PMID:8642349 PMID:8662823

    Open questions at the time
    • Endogenous proteolytic generation of truncated antagonist not demonstrated in vivo
    • Receptor mediating eosinophil recruitment defined only by shared competition
  5. 1999 High

    Characterizing CCR5 engagement revealed that CCL7 can act as a natural receptor antagonist, binding without signaling and blocking agonist responses.

    Evidence Radioligand competition, calcium flux, chemotaxis, internalization and HIV infection assays in CCR5 transfectants

    PMID:10477718

    Open questions at the time
    • Physiological relevance of CCR5 antagonism in vivo not established
    • Weak HIV-inhibitory activity not therapeutically pursued here
  6. 2002 High

    In vivo neutralization studies established CCL7 as a non-redundant driver of both eosinophil and neutrophil recruitment in airway inflammation, identifying epithelium and endothelium as sources.

    Evidence Mouse OVA, ozone and schistosomal granuloma models with anti-CCL7 neutralization, IHC source localization, IL-4 regulation in cultured endothelium

    PMID:11777981 PMID:12107110 PMID:9144514

    Open questions at the time
    • Receptor used on recruited neutrophils not resolved at this stage
    • Relative contribution of epithelial vs endothelial source unclear
  7. 2008 High

    Genetic knockout and pathway studies defined CCL7's tissue-homeostatic and regulatory roles beyond inflammation, including additive monocyte recruitment with CCL2, dopamine neuron differentiation, and fibroblast collagen production.

    Evidence CCL7-KO Listeria model with monocyte flow cytometry; ventral midbrain precursor cultures with Nurr1-KO; fibroblast collagen/TGFβ and OSM-MAPK studies

    PMID:18420193 PMID:18453605 PMID:18981157 PMID:19038247

    Open questions at the time
    • Single-knockout phenotypes incompletely recapitulate CCR2 loss, indicating redundancy
    • Direct receptor on dopaminergic precursors inferred from expression
  8. 2009 High

    Defining cytokine-driven induction pathways established how CCL7 expression is controlled in glia and during fungal infection, and confirmed functional redundancy with CCL2 via CCR2 in suppressing Th2 responses.

    Evidence Rat astrocyte cultures with NFκB/MAPK inhibitors; CCL2-KO/CCR2-KO mice with CCL7 neutralization and IL-4 readouts in Histoplasma infection

    PMID:19577550 PMID:19587014

    Open questions at the time
    • Astrocyte signaling defined pharmacologically, not genetically
    • Mechanism by which CCR2 limits IL-4 not fully resolved
  9. 2014 High

    Biophysical and post-transcriptional studies answered how CCL7 achieves receptor promiscuity and GAG binding as a monomer and how its abundance is fine-tuned, identifying distributed GAG epitopes and let-7d regulation.

    Evidence Hydroxyl radical footprinting, mutagenesis and SPR with heparan sulfate; luciferase 3'UTR reporter and rescue assays for let-7d in RCC

    PMID:24727473 PMID:25193015

    Open questions at the time
    • In vivo consequence of GAG-binding mutations not tested
    • let-7d regulation shown in one tumor context
  10. 2016 Medium

    Cancer studies established CCL7 as a stromal- and tumor-derived driver of invasion and metastasis through defined receptor-effector axes (CCR1/CCR3) and MAPK signaling.

    Evidence CAF/OSCC co-culture with CCR1/CCR3 neutralization; CCL7 overexpression in colon cancer with ERK/JNK inhibitors and xenografts; psoriasis source/blockade studies

    PMID:19937793 PMID:25828150 PMID:27167205

    Open questions at the time
    • Receptor usage varies across tumor types without unifying model
    • Single-lab xenograft systems
  11. 2020 High

    Genetic and mechanistic studies resolved divergent context-dependent roles—antitumor cDC1 recruitment, neutrophil suppression, pro-tumor RhoA-MMP-9 invadopodia maturation, dormancy escape, and sterile injury inflammation.

    Evidence CCL7-KO KP/KL lung tumor and reconstitution; CCL7-KO Leishmania model with add-back; RhoA dominant-negative/CA rescue invadopodia assays; CCR2-Co-IP dormancy model; B cell-derived CCL7 AKI model; PAR1/MDSC studies

    PMID:23972264 PMID:30671055 PMID:32217106 PMID:32737150 PMID:33257678 PMID:33986252 PMID:36685592

    Open questions at the time
    • Determinants selecting pro- vs anti-inflammatory/tumor outcome not defined
    • Receptor-specific signaling bifurcations incompletely mapped
  12. 2021 Medium

    Mechanistic dissection linked CCL7 to macrophage polarization, chromatin-level transcriptional control, and glial neuroinflammation, broadening its role to metabolic and epigenetic reprogramming.

    Evidence CCR1/JAK2/STAT1 macrophage M1 studies in AAA; hepatocyte BRG1-AP-1 redox-sensitive transcription with Co-IP/ChIP; astrocyte-microglia CCL7 in TBI

    PMID:34189838 PMID:34293712 PMID:34454163

    Open questions at the time
    • BRG1-AP-1 axis shown in liver only
    • Glial source mechanisms largely correlative
  13. 2024 High

    Endothelial-focused genetic studies established CCL7 as a regulator of vascular function and macrophage metabolic reprogramming via CCR3 and CCR1 signaling.

    Evidence EC-specific and global Ccl7 KO in diabetic models with AKT-eNOS pathway analysis; sepsis model with CCR1-KO, KAT2A/STAT1 succinylation and ChIP-based glycolytic gene readouts

    PMID:39231238 PMID:40755420

    Open questions at the time
    • Succinylation mechanism reported at abstract-level detail
    • Translation of endothelial CCL7 axis to human disease not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • The molecular determinants that switch CCL7 between agonist and antagonist behavior at shared receptors, and between pro- and anti-inflammatory or pro- and antitumor outcomes in different tissues, remain unresolved.
  • No unifying model linking receptor choice to functional outcome
  • Structural basis of biased signaling not defined
  • In vivo relevance of natural antagonism untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 4
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1500931 Cell-Cell communication 3
Partners
CCR1CCR2CCR3CCR5

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 CCL7 (MCP-3/NC28) was molecularly cloned and identified as a CC chemokine with chemotactic activity for monocytes but not neutrophils; unlike MCP-1, the secreted MCP-3 protein is N-glycosylated. Expression is induced by PMA in U937 cells and super-induced by cycloheximide, and co-regulated with MCP-1 by IFN-γ and IL-13 in PBMC. cDNA cloning, recombinant protein expression, chemotaxis assay, glycosylation analysis, Northern blot/mRNA regulation studies European cytokine network High 8318676
1994 Mouse MCP-3 was identified as the MARC/FIC protein; a cDNA library from LPS-stimulated WEHI-3 macrophages yielded a sequence identical to mouse MARC, establishing MARC/FIC as the murine orthologue of human CCL7. cDNA library screening with human MCP-3 probe, sequencing Biochemical and biophysical research communications Medium 8002978
1995 CCL7 (MCP-3) binds CCR1 (C-C CKR1) as a functional high-affinity receptor: recombinant CCR1-expressing 293 cells bound 125I-MCP-3, MCP-3 induced directional migration of CCR1/293 cells, and MCP-3, MIP-1α, and RANTES cross-competed for binding and cross-desensitized migration responses. Stable transfection of CCR1 cDNA in HEK293 cells, 125I-radioligand binding competition, in vitro chemotaxis assay, calcium flux/desensitization The Journal of biological chemistry High 7545673
1995 CCL7 (MCP-3) binds monocytes with high affinity (Kd ~1–3 nM, ~10,000 sites/cell) and signals through multiple CC chemokine receptors shared with MIP-1α, RANTES, and MCP-1, but also through receptor sites unique to MCP-3 (including sites shared with MIP-1β); MCP-3 was the only CC chemokine that consistently chemoattracted neutrophils in this study, implying a unique receptor on neutrophils. 125I-MCP-3 radioligand binding on primary monocytes and neutrophils, calcium flux cross-desensitization, in vitro chemotaxis European journal of immunology High 7589134
1996 Murine CCR2 (mCCR2) was cloned and shown to bind mouse FIC (mouse CCL7) with high affinity; 125I-JE (mMCP-1) binding to mCCR2-expressing HEK293 cells was competed by FIC but not by MIP-1α, C10, or N51/KC, establishing mCCR2 as a functional receptor for mouse CCL7. cDNA cloning, stable expression in HEK293 cells, 125I radioligand binding competition The Journal of biological chemistry High 8662823
1996 N-terminally truncated CCL7 analog MCP-3(10–76) acts as a multi-receptor antagonist: it binds CCL7, MCP-1, and RANTES binding sites on THP-1 monocytes with high affinity but lacks chemotactic activity, inhibiting responses to all three chemokines, demonstrating that the N-terminus of CCL7 is critical for receptor activation but not binding. Radioligand binding competition on THP-1 cells, in vitro chemotaxis, enzyme release assay The Journal of biological chemistry High 8631850
1996 CCL7 (MCP-4 comparison study) acts as a potent chemoattractant for monocytes and T lymphocytes via shared MCP-1/MCP-3/RANTES receptors, and for eosinophils via eotaxin-shared receptors, establishing CCL7's broad receptor promiscuity across leukocyte subsets. Radioligand binding cross-competition, chemotaxis assay, cross-desensitization on purified leukocyte populations The Journal of experimental medicine Medium 8642349
1997 CCL7 (MCP-3/FIC) is expressed predominantly in airway epithelium after allergen challenge; pre-treatment with anti-MCP-3/FIC antibody significantly inhibited OVA-induced eosinophilia in bronchoalveolar lavage (46% eosinophils in control vs 8% with anti-CCL7), establishing a functional role for CCL7 in eosinophil recruitment in allergic airway inflammation. Mouse OVA sensitization/challenge model, immunocytochemistry for cellular source, RT-PCR, antibody neutralization in vivo, BAL differential cell counts Journal of immunology High 9144514
1999 CCL7 (MCP-3) binds CCR5 with high affinity (IC50 ~2.14 nM competing 125I-MIP-1β) but acts as a natural antagonist: it binds CCR5 without inducing functional responses (calcium flux, chemotaxis), fails to cause CCR5 endocytosis, and inhibits CCR5 activation by MIP-1β. It was a weak inhibitor of HIV infection despite blocking gp120 binding. Radioligand (125I-MIP-1β) competition binding on CCR5-stable transfectants, calcium flux assay, chemotaxis assay, receptor internalization assay, HIV infection inhibition assay Blood High 10477718
2002 CCL7 orchestrates oxidative stress-induced neutrophilic airway inflammation: ozone exposure up-regulated CCL7 protein in lung with airway epithelium as primary source; anti-CCL7 antibody decreased neutrophil recruitment by 63%, establishing a non-redundant role for CCL7 in neutrophil (not only monocyte) recruitment in vivo. Mouse ozone-exposure model, lung mRNA/protein quantification by RT-PCR/ELISA, IHC for cellular source, in vivo antibody neutralization, BAL differential cell counting Journal of immunology High 11777981
2002 CCL7 (MCP-3) contributes 40–50% of eosinophil recruitment in type-2 (Th2-mediated, schistosomal antigen) pulmonary granulomas; endothelial cells in and near granulomas are a major in situ source of CCL7, and IL-4 drives maximal CCL7 expression from cultured mouse lung endothelial cells. Mouse pulmonary granuloma model, in vivo antibody neutralization, immunohistochemistry for source, IL-4 neutralization, cultured endothelial cell MCP-3 production assay The American journal of pathology High 12107110
2008 CCL7 and MCP-1 (CCL2) provide additive, parallel contributions to CCR2-mediated Ly6C(high) inflammatory monocyte recruitment from bone marrow during Listeria monocytogenes infection; MCP-3−/− mice had fewer splenic and circulating Ly6C(high) monocytes, increased bone marrow monocytes, and fewer Tip-DCs, paralleling MCP-1−/− phenotype but not fully recapitulated by either single knockout. CCL7 knockout mice, L. monocytogenes infection model, flow cytometry for monocyte subsets, intracellular cytokine staining for Tip-DCs, bacterial burden quantification Journal of immunology High 18453605
2008 CCL7 and CCL2 selectively promote differentiation of Nurr1+ precursors into midbrain dopamine neurons and enhance neuritogenesis, acting via CCR1 and CCR2 expressed in the ventral midbrain; CCL7 expression is developmentally regulated and reduced in Nurr1 knockout mice. Primary ventral midbrain precursor cultures, CCL2/CCL7 treatment, immunofluorescence for TH+ neurons, Nurr1-KO mouse analysis, developmental mRNA expression analysis Experimental cell research Medium 18420193
2008 CCL7 (MCP-3) promotes type I collagen secretion by fibroblasts through activation of TGFβ signaling/MAPK pathways; TGFβ1 in turn stimulates CCL7 gene expression in fibroblasts, creating a positive feedback loop; microarray analysis confirmed additive effects on key TGFβ-regulated transcripts (PAI-1, OSF2, IGFBP6). Recombinant MCP-3 treatment of fibroblasts, collagen secretion assay, MAPK pathway inhibitor experiments, TGFβ signaling analysis (Smad phosphorylation), microarray, qRT-PCR Experimental cell research Medium 19038247
2009 IL-1β and TNF-α stimulate CCL7 protein production in rat astrocytes through NFκB and p38/JNK MAPK pathways (but not ERK); selective inhibitors of NFκB (MG-132, SC-514) and p38/JNK (SB203580, SP600125) blocked cytokine-induced CCL7 upregulation, establishing signaling pathways for astrocytic CCL7 induction. Primary rat astrocyte cultures, ELISA for CCL7/CCL2, selective pharmacological inhibitors of NFκB (MG-132, SC-514) and MAPK pathways Brain research Medium 19577550
2009 CCL7 and CCL2 together regulate the CCR2 pathway to limit IL-4 generation and control host resistance to Histoplasma capsulatum: CCL7 neutralization in CCL2−/− mice (but not wild-type) resulted in increased IL-4 production and elevated fungal burden, demonstrating functional redundancy between CCL7 and CCL2 via CCR2 in suppressing Th2 responses. CCL2-KO mice, CCR2-KO mice, in vivo CCL7 antibody neutralization, IL-4 ELISA/intracellular staining, arginase/YM1 transcription analysis, fungal burden quantification Journal of immunology High 19587014
2010 CCL7 is markedly upregulated in carcinoma-associated fibroblasts (CAFs) co-cultured with oral squamous cell carcinoma (OSCC) cells; recombinant CCL7 promoted OSCC invasion and migration, and this was inhibited by CCL7 neutralizing antibody or anti-CCR1/anti-CCR3 antibodies, establishing CCL7-CCR1/CCR3 signaling as the axis for CAF-mediated cancer invasion. Microarray of co-culture vs monoculture, qRT-PCR, ELISA, invasion/migration assays, neutralizing antibody treatments, RT-PCR for receptor expression on cancer cells International journal of cancer Medium 19937793
2012 TLR9 signaling promotes early induction of CCL7 (but not CCL2) in the lung during Cryptococcus neoformans infection; CCL7 reconstitution in TLR9-deficient mice restored CD11b+ dendritic cell accumulation, IFN-γ production, and effector cell recruitment, placing CCL7 downstream of TLR9 in the afferent phase of antifungal immunity. TLR9-KO mice, C. neoformans lung infection, CCL7 reconstitution by intratracheal administration, flow cytometry for immune cell subsets, cytokine ELISA, fungal burden Journal of immunology High 22422883
2014 CCL7 has multiple glycosaminoglycan (GAG)-binding epitopes distributed across its surface (identified by hydroxyl radical footprinting and mutagenesis), enabling it to bind heparan sulfate with high affinity (~equivalent to CCL2) as a functional monomer without oligomerization; this is distinct from CCL2, which requires oligomerization for full GAG binding affinity. Hydroxyl radical footprinting (mass spectrometry), site-directed mutagenesis, surface plasmon resonance with heparan sulfate The Journal of biological chemistry High 24727473
2014 Let-7d directly targets the 3'UTR of CCL7 mRNA; let-7d overexpression in renal cell carcinoma cells reduced CCL7 protein, suppressed PBMC recruitment in vitro and tumor macrophage infiltration in vivo; exogenous CCL7 reversed let-7d-mediated inhibition of migration and PBMC recruitment, establishing CCL7 as a direct target of let-7d regulation. Luciferase 3'UTR reporter assay for let-7d targeting, qRT-PCR, cell migration/PBMC recruitment assays, xenograft mouse models, rescue experiments with exogenous CCL7 Molecular cancer Medium 25193015
2015 CCL7 in rhinovirus 1B infection drives neutrophil and macrophage influx into lungs and activates NF-κB p65/p50 subunits and airway hyperreactivity; CCL7 neutralization reduced NF-κB activation and airway hyperreactivity in non-allergic mice, linking CCL7 to NF-κB-mediated inflammation downstream of rhinovirus infection. In vivo murine RV1B infection, anti-CCL7 antibody neutralization, NF-κB subunit activation assay, lung function measurement (airway hyperreactivity), flow cytometry for leukocyte influx Journal of immunology Medium 25847975
2016 CCL7 signals through CCR3 on colon cancer cells to promote EMT, cellular proliferation, invasion, and migration via ERK and JNK signaling pathways; CCL7-overexpressing HCT116/HT29 cells showed enhanced liver and lung metastasis in orthotopic mouse models. CCL7 overexpression in colon cancer cell lines, in vitro invasion/migration/proliferation assays, ERK/JNK pathway inhibitor experiments, ectopic and orthotopic mouse xenograft models Oncotarget Medium 27167205
2019 Intrathecal injection of CCL7 induced dose-dependent pain-related behavior in naive mice; intrathecal neutralizing anti-CCL7 antibody attenuated CCI-induced neuropathic pain and augmented morphine/buprenorphine analgesia; spinal CCL7 is produced by both microglia and astrocytes after sciatic nerve injury, placing CCL7 in the spinal nociceptive signaling axis. Chronic constriction injury (CCI) mouse model, intrathecal CCL7 injection (dose-response), intrathecal anti-CCL7 antibody, von Frey and cold plate pain tests, qRT-PCR for CCL7 in spinal cord, primary glial cell cultures Cytokine Medium 31003094
2019 CCL7 directly antagonizes neutrophil migration in vitro and negatively regulates neutrophil recruitment in Leishmania major-infected skin in vivo; CCL7-deficient mice showed enhanced neutrophilic infiltration with elevated IL-17 gene profile, and CCL7 add-back specifically reduced neutrophil influx, revealing a non-redundant role for CCL7 in limiting neutrophilic inflammation. CCL7-KO mice, L. major infection model, in vitro neutrophil migration assay with CCL7, in vivo CCL7 reconstitution, flow cytometry, cytokine profiling, parasite burden Frontiers in immunology High 30671055
2019 Irisin promotes C2C12 myoblast proliferation through ERK phosphorylation–dependent upregulation of CCL7; CCL7 knockdown suppressed irisin-induced proliferation, placing CCL7 as a downstream effector of irisin-ERK signaling in myoblast proliferation. Irisin treatment of C2C12 cells, ERK inhibitor (U0126), transcriptomic analysis, qRT-PCR, CCL7 siRNA knockdown, proliferation assays (Pcna, Mki67, Mcm2) PloS one Medium 31518371
2020 CCL7 recruits conventional DC1 (cDC1) into the lung tumor microenvironment to promote CD8+ and CD4+ T cell expansion; CCL7-deficient KP mice showed impaired cDC1 infiltration and T cell expansion, and CCL7 administration alone or with anti-PD-1 inhibited tumor development, establishing CCL7 as a cDC1-recruiting chemokine that enhances checkpoint immunotherapy. CCL7-KO in KrasLSL-G12D/Tp53fl/fl (KP) and KrasLSL-G12D/Lkb1fl/fl (KL) mouse models, flow cytometry, intratracheal CCL7 administration, anti-PD-1 combination therapy, survival analysis Nature communications High 33257678
2020 B lymphocytes (particularly B220low innate B cells) produce CCL7 to recruit neutrophils and monocytes to the injured kidney; CCL7 blockade in mice reduced myeloid cell infiltration and ameliorated acute kidney injury, establishing B cell-derived CCL7 as a driver of sterile innate inflammation in AKI. Mouse AKI model, flow cytometry for B cell subsets and myeloid cells, B cell CCL7 production measurement, Siglec-G-deficient mice (increased innate B cells), in vivo CCL7 antibody blockade, human AKI patient cohort urinary CCL7 levels Journal of immunology High 32737150
2020 SOX18 directly transactivates CCL7 promoter; CCL7 and CCR1 form a positive feedback loop (CCL7-CCR1-ERK/ELK1-SOX18) promoting gastric cancer invasion and metastasis; CCL7/MCAM knockdown reduced SOX18-mediated invasion, and CCR1 inhibitor BX471 suppressed SOX18-mediated metastasis. ChIP assay, luciferase reporter, CCL7/MCAM knockdown and overexpression, invasion/migration assays, ERK/ELK1 pathway inhibition, in vivo mouse metastasis models, BX471 (CCR1 inhibitor) treatment Oncogene Medium 32616889
2020 CCL7 and CCL2 redundantly mediate migration of CCR2+/CX3CR1+ immunosuppressive M-MDSCs into the glioblastoma tumor microenvironment via CCR2; combined neutralization of CCL2 and CCL7 completely blocked CCR2-expressing cell migration to glioma-conditioned media, while single knockdown of either was insufficient. Bone marrow-derived MDSC migration assays with recombinant CCL2/CCL7, KR158B glioma CCL2/CCL7 knockdown, CCL2+CCL7 combined neutralization antibody, flow cytometry for tumor-infiltrating MDSCs in vivo Frontiers in immunology Medium 36685592
2021 BRG1 (a chromatin remodeling protein) interacts with AP-1 to drive CCL7 transcription in hepatocytes in a redox-sensitive manner; BRG1 hepatocyte-specific deletion abolished CCL7 induction and macrophage infiltration in liver injury models; CK2-catalyzed phosphorylation of BRG1 mediates this regulation, and the process is blocked by the antioxidant N-acetylcysteine. Hepatocyte-specific BRG1 conditional KO mice, LPS/MCD diet liver injury models, in vitro LPS/palmitate treatment of hepatocytes, Co-IP (BRG1-AP-1 interaction), pharmacological inhibition (N-acetylcysteine), ChIP, macrophage migration assay Redox biology High 34454163
2021 CCL7 promotes M1 macrophage polarization via CCR1/JAK2/STAT1 signaling; in vivo CCL7-neutralizing antibody reduced macrophage infiltration and attenuated angiotensin II-induced abdominal aortic aneurysm; JAK2/STAT1 inhibition blocked CCL7-induced M1 activation in macrophages. Ang II mouse AAA model, ex vivo macrophage polarization assays, CCR1 blockade, JAK2/STAT1 inhibitor, in vivo CCL7-neutralizing antibody treatment, histology/immunostaining Journal of cellular and molecular medicine Medium 34189838
2021 Astrocyte-derived CCL7 promotes microglial activation and pro-inflammatory cytokine release after traumatic brain injury; CCL7 knockout improved microglia-controlled inflammation and neurological outcomes; CCL7-siRNA attenuated LPS-induced pro-inflammatory markers in astrocyte-microglia co-cultures. Rat TBI model, CCL7-KO, in vitro LPS-stimulated astrocyte-microglia co-cultures with CCL7-siRNA, cytokine/marker quantification, neurological scoring International immunopharmacology Medium 34293712
2024 CCL7 impairs endothelial function through CCR3 via downregulation of AKT-eNOS and AKT/NRF2/HO-1/VEGF/SDF-1 pathways and upregulation of ERK/NF-κB/IL-1β/IL-6/TNF-α pathways; CCL7 is induced in endothelial cells by high glucose through c-Fos/c-Jun signaling; endothelial cell-specific Ccl7 knockout in STZ-diabetic mice ameliorated vasculopathy, neovasculogenesis, and wound repair. CCL7 KD/neutralization in endothelial cells, recombinant CCL7 treatment, specific pathway inhibitors (AKT, ERK, NF-κB), Ccl7 global KO and endothelial cell-specific KO mice in STZ/db/db/HFD DM models, tube formation/migration assays, in vivo ischemia/wound models, flow cytometry for circulating EPCs Science translational medicine High 39231238
2025 Endothelial cell-derived CCL7 signals via CCR1 on macrophages to upregulate KAT2A expression, which catalyzes STAT1 succinylation; this epigenetic modification increases STAT1 binding to glycolytic gene promoters, driving metabolic reprogramming (enhanced glycolysis) and M1 polarization in macrophages, promoting septic acute lung injury; Ccr1-KO mice showed attenuated lung inflammation. EC-specific CCL7 inhibition in sepsis model, CCR1-KO mice, KAT2A expression analysis, STAT1 succinylation assay, ChIP for STAT1 binding to glycolytic gene promoters, metabolic flux assay, macrophage polarization assay Advanced science Medium 40755420
2020 CCL7 secreted by Mo-MDSCs binds CCR2 on colorectal cancer micro-metastatic cells and activates JAK/STAT3 pathway to break dormancy and promote metastatic outgrowth; Co-immunoprecipitation confirmed CCL7-CCR2 co-localization; CCL7 inhibition maintained CRC cells in dormancy and reduced metastasis. Co-immunoprecipitation (CCL7-CCR2 interaction), in vitro dormancy cell models, mouse liver metastasis models, flow cytometry for MDSCs, qRT-PCR/Western blot for JAK/STAT3, in vivo CCL7/MDSC inhibitor administration Cell death & disease Medium 33986252
2020 CCL7 regulates invadopodia maturation by promoting MMP-9 targeting to the invadopodia complex via RhoA signaling; dominant-negative RhoA blocked CCL7/CCR3-induced invadopodia maturation and collagen degradation, while constitutively active RhoA rescued maturation in CCL7-silenced cells; ERK and PI3K pathways regulated the initiation (not maturation) stage. CCL7 siRNA in cancer cells, dominant-negative and constitutively active RhoA overexpression, MMP-9 localization by immunofluorescence, invadopodia/collagen degradation assay, ERK/PI3K inhibitors, in vivo metastasis assay Cancer letters Medium 32217106
2022 MSC-secreted CCL7 activates CCR1 on colorectal cancer cells, which downstream activates CBP/P300 to acetylate KLF5, promoting CXCL5 transcription; TGF-β (also secreted by MSCs) inhibits this process by regulating SMAD4 to suppress KLF5 transcriptional activation. Co-culture of MSCs with CRC cells, CCL7/CCR1 neutralization/inhibition, ChIP for KLF5-CXCL5 promoter binding, CBP/P300 acetylation assay, TGF-β/SMAD4 pathway analysis, in vivo CRC metastasis models Molecular therapy Medium 35283273
2008 Oncostatin M (OSM) stimulates CCL7 and CCL8 expression in primary human dermal fibroblasts via ERK1/2 and p38 MAPK pathways, with p38 prolonging CCL7 mRNA half-life through inhibition of tristetraprolin; constitutive JAK2/STAT5 activation suppressed CCL1 but NOT CCL7 expression, demonstrating that CCL7 transcription is MAPK-dependent but STAT5-independent in fibroblasts. Primary human dermal fibroblast stimulation with OSM, selective MAPK inhibitors, STAT transcription factor knockdown, tristetraprolin studies, mRNA stability assays Journal of immunology Medium 18981157
2014 PAR1 antagonism reduces acute LPS-induced neutrophilic lung inflammation by suppressing CCL2 and CCL7 expression (but not CXCL1/CXCL2 or TNF/IL-6); antibody neutralization of both CCL2 and CCL7 reduced LPS-induced leukocyte and neutrophil accumulation; CCL7 was localized by IHC specifically to pulmonary epithelium; intranasal recombinant CCL7 alone recruited neutrophils to airspaces; lung neutrophils had increased CCR1/CCR2 and decreased CXCR2 compared to circulating neutrophils. Mouse LPS lung inflammation model, PAR1 antagonist treatment, antibody neutralization of CCL2/CCL7, IHC for cellular source, intranasal recombinant CCL7 administration, flow cytometry for chemokine receptor expression on neutrophils American journal of respiratory cell and molecular biology High 23972264
2016 CCL7 in psoriatic lesional skin is markedly upregulated compared to other chemokines; keratinocytes and dermal blood endothelial cells are its cellular sources; CCL7 blockade in imiquimod-induced psoriasis-like mouse model reduced myeloid inflammation and key cytokines (CCL20, IL-12p40, IL-17C) and increased IL-4; TNF-α blocker infliximab downregulated CCL7 within 16 hours in human lesional skin, placing CCL7 downstream of TNF-α in Th1/Th17 inflammation. Quantitative RT-PCR in human skin biopsies, imiquimod mouse model with CCL7 blockade, infliximab human clinical sample analysis, cytokine profiling Experimental dermatology Medium 25828150

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19. The Journal of allergy and clinical immunology 521 32360286
1998 MCP-1, MCP-2 and MCP-3 expression in multiple sclerosis lesions: an immunohistochemical and in situ hybridization study. Journal of neuroimmunology 307 9655469
1999 Increased expression of IP-10, IL-8, MCP-1, and MCP-3 in ulcerative colitis. The American journal of pathology 230 10433925
1999 CCR5 binds multiple CC-chemokines: MCP-3 acts as a natural antagonist. Blood 230 10477718
2009 The fic domain: regulation of cell signaling by adenylylation. Molecular cell 220 19362538
2008 Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. Journal of immunology (Baltimore, Md. : 1950) 206 18453605
2009 Inflammatory cytokines stimulate the chemokines CCL2/MCP-1 and CCL7/MCP-3 through NFkB and MAPK dependent pathways in rat astrocytes [corrected]. Brain research 186 19577550
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2016 Crosstalk between CCL7 and CCR3 promotes metastasis of colon cancer cells via ERK-JNK signaling pathways. Oncotarget 90 27167205
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1995 Monocyte chemotactic protein-3 (MCP3) interacts with multiple leukocyte receptors: binding and signaling of MCP3 through shared as well as unique receptors on monocytes and neutrophils. European journal of immunology 77 7589134
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2003 MCP-1-MCP-3-Eotaxin gene cluster influences HIV-1 transmission. AIDS (London, England) 61 14571188
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1996 Increased expression of mRNA encoding RANTES and MCP-3 in the bronchial mucosa in atopic asthma. The European respiratory journal 50 8980953
2023 Glioma-derived CCL2 and CCL7 mediate migration of immune suppressive CCR2+/CX3CR1+ M-MDSCs into the tumor microenvironment in a redundant manner. Frontiers in immunology 49 36685592
2014 Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions. Structure (London, England : 1993) 47 25435325
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2016 The Caenorhabditis elegans Protein FIC-1 Is an AMPylase That Covalently Modifies Heat-Shock 70 Family Proteins, Translation Elongation Factors and Histones. PLoS genetics 43 27138431
2012 Early induction of CCL7 downstream of TLR9 signaling promotes the development of robust immunity to cryptococcal infection. Journal of immunology (Baltimore, Md. : 1950) 43 22422883
2017 Fic-mediated deAMPylation is not dependent on homodimerization and rescues toxic AMPylation in flies. The Journal of biological chemistry 42 29089387
2014 Multiple glycosaminoglycan-binding epitopes of monocyte chemoattractant protein-3/CCL7 enable it to function as a non-oligomerizing chemokine. The Journal of biological chemistry 42 24727473
2008 The beta-chemokines CCL2 and CCL7 are two novel differentiation factors for midbrain dopaminergic precursors and neurons. Experimental cell research 42 18420193
2021 CCL7 contributes to angiotensin II-induced abdominal aortic aneurysm by promoting macrophage infiltration and pro-inflammatory phenotype. Journal of cellular and molecular medicine 41 34189838
2007 MCP-3 (CCL7) delivered by parvovirus MVMp reduces tumorigenicity of mouse melanoma cells through activation of T lymphocytes and NK cells. International journal of cancer 41 17154174
2021 Astrocyte-derived CCL7 promotes microglia-mediated inflammation following traumatic brain injury. International immunopharmacology 40 34293712
2015 CCL7 and IRF-7 Mediate Hallmark Inflammatory and IFN Responses following Rhinovirus 1B Infection. Journal of immunology (Baltimore, Md. : 1950) 40 25847975
2003 Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2, CCL5, CCL7, and CCL8. Journal of leukocyte biology 40 12885941
2019 Alpha-Synuclein Is a Target of Fic-Mediated Adenylylation/AMPylation: Possible Implications for Parkinson's Disease. Journal of molecular biology 39 31034889
2014 MiR-506 inhibits PRRSV replication in MARC-145 cells via CD151. Molecular and cellular biochemistry 39 24878990
2020 B Lymphocyte-Derived CCL7 Augments Neutrophil and Monocyte Recruitment, Exacerbating Acute Kidney Injury. Journal of immunology (Baltimore, Md. : 1950) 38 32737150
2019 CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection. Frontiers in immunology 38 30671055
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2006 Serum levels of monocyte chemotactic protein-3/CCL7 are raised in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. Annals of the rheumatic diseases 38 16344498
2020 SOX18 promotes gastric cancer metastasis through transactivating MCAM and CCL7. Oncogene 37 32616889
2021 Redox-sensitive activation of CCL7 by BRG1 in hepatocytes during liver injury. Redox biology 36 34454163
2002 Eosinophil recruitment in type-2 hypersensitivity pulmonary granulomas: source and contribution of monocyte chemotactic protein-3 (CCL7). The American journal of pathology 36 12107110
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2022 CCL7 and TGF-β secreted by MSCs play opposite roles in regulating CRC metastasis in a KLF5/CXCL5-dependent manner. Molecular therapy : the journal of the American Society of Gene Therapy 34 35283273
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2021 Inhibition of CCL7 derived from Mo-MDSCs prevents metastatic progression from latency in colorectal cancer. Cell death & disease 33 33986252
2020 The chemokine CCL7 regulates invadopodia maturation and MMP-9 mediated collagen degradation in liver-metastatic carcinoma cells. Cancer letters 33 32217106
2016 Biological Diversity and Molecular Plasticity of FIC Domain Proteins. Annual review of microbiology 33 27482742
2013 Conserved inhibitory mechanism and competent ATP binding mode for adenylyltransferases with Fic fold. PloS one 33 23738009
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2022 LINC01094/SPI1/CCL7 Axis Promotes Macrophage Accumulation in Lung Adenocarcinoma and Tumor Cell Dissemination. Journal of immunology research 30 36118415
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2015 Expression and Function of mARC: Roles in Lipogenesis and Metabolic Activation of Ximelagatran. PloS one 28 26378779
2008 Oncostatin M-induced and constitutive activation of the JAK2/STAT5/CIS pathway suppresses CCL1, but not CCL7 and CCL8, chemokine expression. Journal of immunology (Baltimore, Md. : 1950) 28 18981157
2008 Cross-talk between MCP-3 and TGFbeta promotes fibroblast collagen biosynthesis. Experimental cell research 28 19038247
1988 Cloning of the fic-1 gene involved in cell filamentation induced by cyclic AMP and construction of a delta fic Escherichia coli strain. Journal of bacteriology 28 2842288
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2017 Upregulation of CCL7 and CCL2 in reward system mediated through dopamine D1 receptor signaling underlies methamphetamine-induced place preference in mice. Neuroscience letters 27 29174638
2011 MCP-3/CCL7 production by astrocytes: implications for SIV neuroinvasion and AIDS encephalitis. Journal of neurovirology 26 21279498
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2016 Intrinsic regulation of FIC-domain AMP-transferases by oligomerization and automodification. Proceedings of the National Academy of Sciences of the United States of America 24 26787847
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2013 Dual effect of chemokine CCL7/MCP-3 in the development of renal tubulointerstitial fibrosis. Biochemical and biophysical research communications 23 23872063
2022 The role of CCL2, CCL7, ICAM-1, and VCAM-1 in interaction of endothelial cells and natural killer cells. International immunopharmacology 22 36274485
2016 Role of CCL7 in Type I Hypersensitivity Reactions in Murine Experimental Allergic Conjunctivitis. Journal of immunology (Baltimore, Md. : 1950) 22 27956527
2024 Inhibition of CCL7 improves endothelial dysfunction and vasculopathy in mouse models of diabetes mellitus. Science translational medicine 21 39231238
2025 Endothelial-Derived CCL7 Promotes Macrophage Polarization and Aggravates Septic Acute Lung Injury via CCR1-Mediated STAT1 Succinylation. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20 40755420
2023 HDAC2 exacerbates rheumatoid arthritis progression via the IL-17-CCL7 signaling pathway. Environmental toxicology 20 37021908
2022 Fic-mediated AMPylation tempers the unfolded protein response during physiological stress. Proceedings of the National Academy of Sciences of the United States of America 20 35914137
2020 Identification of targets of AMPylating Fic enzymes by co-substrate-mediated covalent capture. Nature chemistry 20 32632184

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