Affinage

CLC

Galectin-10 · UniProt Q05315

Length
142 aa
Mass
16.5 kDa
Annotated
2026-06-14
38 papers in source corpus 16 papers cited in narrative 16 extracted findings
Cross-family judge vs UniProt: tie

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CLC/galectin-10 is an eosinophil-predominant galectin-family protein whose structural features redirect it from canonical β-galactoside binding toward a distinct ligand chemistry and a set of immune effector functions (PMID:10529229, PMID:29293962). Despite carrying a carbohydrate recognition domain, it is not a lysophospholipase; rather it binds lysophospholipase inhibitors and physically associates with eosinophil lysophospholipases (PMID:11834744). Structurally it forms a novel homodimer in which Glu33 from one subunit occludes the carbohydrate-binding site of the partner subunit, switching specificity away from disaccharides toward mannose and small hydroxylated molecules, with His53 central to ligand contact and Trp72/Trp127 governing ligand binding, dimerization, and nuclear transport (PMID:10529229, PMID:29293962, PMID:30239701). In eosinophils it is stored in the peripheral cytoplasm rather than secretory granules and is not released by classical degranulation; instead it is liberated through EETosis, a ROS- and PAD4-dependent cytolytic cell death that deposits galectin-10 in extracellular traps (PMID:32108369, PMID:33750029). Intracellularly it interacts with granule cationic ribonucleases EDN/RNS2 and ECP/RNS3 in a glycosylation-independent, non-inhibitory manner and is required for eosinophil granulogenesis (PMID:31982451). Functionally, galectin-10 is essential for the anergy and suppressive activity of regulatory T cells and suppressive eosinophils, acting through immune synapses and extracellular traps to inhibit T cell proliferation (PMID:17502455, PMID:28515279, PMID:33080067), and in its crystalline state it potently drives IL-1β-, MAPK-, and NF-κB-dependent inflammatory responses in epithelial and stromal cells (PMID:35274950, PMID:37640566).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1999 High

    Established that despite being a galectin, CLC/Gal-10 does not bind β-galactosides but selectively binds mannose, redefining its ligand chemistry through an altered CRD topology.

    Evidence X-ray crystallography of the CLC–mannose complex at 1.8 Å

    PMID:10529229

    Open questions at the time
    • Biological ligand in vivo not identified
    • Did not address dimerization-dependent occlusion of the site
  2. 2001 Medium

    Defined the transcriptional control of galectin-10, identifying activating and silencing promoter elements and their binding factors.

    Evidence Promoter deletion analysis and supershift EMSA

    PMID:11441910

    Open questions at the time
    • Did not link transcriptional regulation to eosinophil lineage signals
    • No in vivo validation
  3. 2002 High

    Resolved the long-standing 'Charcot-Leyden crystal = lysophospholipase' assumption by showing CLC has no intrinsic lysophospholipase activity but instead binds inhibitors and the actual enzymes.

    Evidence Antibody depletion enzyme assays, crystallography of CLC–inhibitor complexes, ligand blotting

    PMID:11834744

    Open questions at the time
    • Functional consequence of lysophospholipase binding unclear
    • True endogenous physiological activity not established
  4. 2007 Medium

    Identified galectin-10 as a Treg-restricted intracellular protein required for their anergy and suppressive function, extending its role beyond eosinophils.

    Evidence Differential proteomics, flow cytometry, specific inhibition in human Tregs

    PMID:17502455

    Open questions at the time
    • Molecular mechanism of suppression not defined
    • Intracellular target/partner in Tregs unknown
  5. 2017 Medium

    Showed eosinophil galectin-10 is a T cell-suppressive effector that acts via immune synapses and is sufficient as a recombinant protein.

    Evidence Antibody neutralization in coculture, recombinant protein assays, immunofluorescence of synapses

    PMID:28515279

    Open questions at the time
    • Receptor on T cells unidentified
    • Suppression only partially abrogated by neutralization
  6. 2018 High

    Determined that galectin-10 forms a distinct homodimer in which Glu33 occludes the partner's binding site, mechanistically explaining its switched ligand specificity.

    Evidence Crystallography of Gal-10 and eight variants, SEC, hemagglutination, alanine mutagenesis

    PMID:29293962

    Open questions at the time
    • Physiological relevance of mannose/glycerol binding unresolved
    • Dynamics of monomer-dimer equilibrium in cells unknown
  7. 2019 High

    Confirmed dimerization-dependent suppression of carbohydrate binding and assigned Trp127 to dimer interface and Trp72 to nuclear transport.

    Evidence Crystallography of E33A, binding assays, EGFP-tagged localization in HeLa, mutagenesis

    PMID:30239701

    Open questions at the time
    • Functional purpose of nuclear localization not established
    • Endogenous trigger for monomer/dimer switching unknown
  8. 2020 High

    Defined galectin-10's intracellular partnership with eosinophil cationic RNases and its requirement for granulogenesis, linking it to granule biogenesis.

    Evidence Reciprocal co-IP/affinity purification, shRNA knockdown in CD34+ progenitor model, confocal imaging

    PMID:31982451

    Open questions at the time
    • Mechanism by which it aids RNase packaging unclear
    • Whether interaction is direct or bridged not resolved
  9. 2020 High

    Established that galectin-10 resides in the peripheral cytoplasm and is not exported by classical degranulation, reframing its secretion route.

    Evidence Immunonanogold transmission EM with quantitative analysis, immunofluorescence, CCL11/TNF-α stimulation

    PMID:32108369

    Open questions at the time
    • Mechanism anchoring it to plasma membrane microdomains unknown
    • Did not directly observe the release event
  10. 2020 Medium

    Showed that CD16+ suppressive eosinophils release galectin-10 via extracellular trap formation to suppress T cells, identifying a DNA-dependent suppressive mechanism.

    Evidence Confocal microscopy, imaging flow cytometry, DNase I dissolution, thymidine proliferation assay

    PMID:33080067

    Open questions at the time
    • Suppression only partially DNase-sensitive
    • Eosinophil subset markers driving this not fully defined
  11. 2021 High

    Identified EETosis as the ROS- and PAD4-dependent cytolytic mechanism for galectin-10 release and tied it to disease tissue.

    Evidence In vitro EETosis with ROS/PAD4 inhibitors, EM and immunostaining of EGPA tissue, ELISA

    PMID:33750029

    Open questions at the time
    • Upstream triggers of EETosis in disease unclear
    • Fate of released galectin-10 in tissue not traced
  12. 2022 Medium

    Demonstrated that the crystalline state, not merely presence, of galectin-10 dictates its inflammatory potency in airway epithelium.

    Evidence Engineered crystalline vs soluble Gal-10, cytokine gene expression in primary cells and nasal polyps

    PMID:35274950

    Open questions at the time
    • Receptor/sensor recognizing crystals unidentified
    • In vivo relevance beyond patient tissue not tested here
  13. 2023 Medium

    Showed extracellular galectin-10 activates p38/ERK/JNK signaling to upregulate MMPs in skin cells, extending its pro-inflammatory reach.

    Evidence Recombinant Gal-10 stimulation of keratinocytes/fibroblasts, qPCR, ELISA, WB, pathway inhibition

    PMID:37640566

    Open questions at the time
    • Cell-surface receptor mediating MAPK activation unknown
    • Direct causal link to blister formation not demonstrated
  14. 2025 Medium

    Defined the physicochemical basis of galectin-10 crystallization and demonstrated therapeutic crystal dissolution in vivo.

    Evidence In vitro crystal dissolution assays, murine intratracheal crystal-induced inflammation model

    PMID:39894983

    Open questions at the time
    • Specificity of arginine-rich peptides in vivo not fully characterized
    • Long-term efficacy/safety not assessed
  15. 2025 Low

    Implicated galectin-10 in promoting eosinophilic inflammation through p38 MAPK/NF-κB signaling and cytokine expression.

    Evidence siRNA knockdown in human eosinophils, WB for p-p38/p-p65, ELISA

    PMID:40921147

    Open questions at the time
    • Single-lab siRNA approach without rescue or structural validation
    • Direct vs indirect effect on signaling not separated

Open questions

Synthesis pass · forward-looking unresolved questions
  • The cell-surface receptor(s) mediating galectin-10's extracellular T cell-suppressive and pro-inflammatory effects, and the trigger that governs its monomer/dimer and soluble/crystalline transitions, remain unresolved.
  • No receptor identified for extracellular galectin-10
  • Endogenous control of crystallization in vivo undefined
  • Connection between Treg-intrinsic and eosinophil-secreted functions unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 2
Localization
GO:0005576 extracellular region 1 GO:0005634 nucleus 1 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 1
Partners
RNASE2RNASE3

Evidence

Reading pass · 16 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 CLC protein (galectin-10) is NOT a lysophospholipase: antibody depletion of CLC from eosinophil lysates retained full lysophospholipase activity, and purified CLC protein lacked significant lysophospholipase activity. Instead, CLC protein binds lysophospholipase inhibitors (p-chloromercuribenzenesulfonate via disulfide bonds with Cys29 and Cys57, and N-ethylmaleimide via ring stacking with Trp72 in the carbohydrate recognition domain) and physically interacts with eosinophil lysophospholipases. Antibody affinity chromatography depletion, enzyme activity assays, X-ray crystallography of CLC–inhibitor complexes, ligand blotting The Journal of biological chemistry High 11834744
1999 CLC protein (galectin-10) selectively binds mannose (not β-galactosides) through its carbohydrate recognition domain (CRD); partial conservation of galectin CRD residues results in altered topology and chemistry of the binding site, explaining the switch in carbohydrate specificity. X-ray crystallography of CLC–mannose complex at 1.8 Å resolution Biochemistry High 10529229
2007 Galectin-10 is constitutively and exclusively expressed intracellularly in human CD4+CD25+Foxp3+ regulatory T cells (Tregs) but not in resting or activated conventional CD4+ T cells; specific inhibition of galectin-10 restored proliferative capacity of Tregs and abrogated their suppressive function, establishing galectin-10 as essential for Treg anergy and suppression. Differential proteomics, single-cell staining, flow cytometry, specific inhibition of galectin-10 Blood Medium 17502455
2018 Galectin-10 forms a novel homodimer with a global shape distinct from other prototype galectins (Gal-1, -2, -7); in the dimer, Glu33 from one subunit blocks the carbohydrate-binding site of the other subunit, inhibiting disaccharide binding. Glycerol and small hydroxylated molecules bind the ligand-binding site with His53 being most crucial. Trp72 negatively regulates ligand binding (W72A mutant shows enhanced erythrocyte agglutination). X-ray crystallography of Gal-10 and eight variants (1.55–2.00 Å resolution), size exclusion chromatography, hemagglutination assay, alanine mutagenesis Glycobiology High 29293962
2019 Glu33 in the galectin-10 dimer interface blocks lactose binding; E33A mutant adopts a conformation allowing lactose binding as shown structurally and biochemically. Trp127 at the homodimer interface is essential for dimerization; the W127A monomer shows higher hemagglutination activity and can bind lactose-modified sepharose, confirming that dimerization suppresses carbohydrate binding. Trp72 is required for nuclear transport of Gal-10 (EGFP-tagged W72A cannot be transported into the nucleus in HeLa cells). X-ray crystallography of E33A variant, hemagglutination assay, solid-phase binding assay, EGFP-tagged subcellular localization in HeLa cells, site-directed mutagenesis Glycobiology High 30239701
2020 CLC/Gal-10 interacts with eosinophil granule cationic ribonucleases (eosinophil-derived neurotoxin/RNS2 and eosinophil cationic protein/RNS3) and with murine eosinophil-associated RNases; this interaction is independent of glycosylation and is not inhibitory to endoRNase activity. Knockdown of CLC/Gal-10 in human CD34+ cord blood-derived progenitor eosinophils impairs eosinophil granulogenesis. IFN-γ activation induces rapid colocalization of CLC/Gal-10 with EDN/RNS2 and CD63, suggesting a role in vesicular transport of cationic RNases during degranulation. Ligand blotting, co-immunoprecipitation, co-affinity purification, enzyme activity assays, confocal microscopy, shRNA knockdown in CD34+ progenitor differentiation model The Journal of allergy and clinical immunology High 31982451
2020 CLC-P/Gal-10 is stored predominantly in the peripheral cytoplasm of human eosinophils (within ~250 nm of the plasma membrane) and NOT within secretory (specific) granules; stimulation with CCL11 or TNF-α does not change this peripheral localization, indicating CLC-P/Gal-10 is not exported through classical degranulation (piecemeal degranulation or compound exocytosis). High-density microdomains of CLC-P/Gal-10 interact with the plasma membrane in ~60% of the membrane area. Pre-embedding immunonanogold transmission electron microscopy, quantitative imaging analysis, immunofluorescence, eosinophil activation with CCL11 and TNF-α Journal of leukocyte biology High 32108369
2021 EETosis (eosinophil extracellular trap cell death) is the mechanism for galectin-10 release from eosinophils; EETosis is dependent on reactive oxygen species and PAD4-dependent histone citrullination, resulting in cytolytic release of net-like extracellular traps containing galectin-10, free galectin-10, and membrane-bound intact granules. Loss of cytoplasmic galectin-10 and extracellular deposition are signatures of EETosis in eosinophilic granulomatosis with polyangiitis (EGPA) tissues. In vitro eosinophil EETosis characterization, ROS and PAD4 inhibition assays, immunostaining, electron microscopy of EGPA tissues, ELISA Arthritis & rheumatology (Hoboken, N.J.) High 33750029
2017 Galectin-10 functions as a T cell-suppressive molecule in eosinophils: antibody-mediated neutralization of galectin-10 partially abrogated eosinophil-mediated suppression of T cell proliferation; recombinant galectin-10 alone suppressed T cell proliferation. Galectin-10-containing immune synapses form between eosinophils and lymphocytes. Antibody neutralization in coculture, recombinant protein functional assay, FACS sorting, immunofluorescence imaging of immune synapses Journal of immunology (Baltimore, Md. : 1950) Medium 28515279
2020 CD16+ suppressive eosinophils form galectin-10-containing synapses with T cells, then release galectin-10 via plasma membrane disintegration and extracellular trap formation containing nuclear DNA and galectin-10. DNase I treatment to dissolve extracellular traps partially abrogates T cell suppression by eosinophils. Only CD16-expressing suppressive eosinophils (not conventional CD16neg eosinophils) form these synapses and EETs. Confocal microscopy, imaging flow cytometry, DNase I dissolution assay, [3H]-thymidine proliferation assay Clinical and experimental immunology Medium 33080067
2022 Crystalline (insoluble) galectin-10 has significantly greater potency to induce inflammatory chemokine/cytokine release (IL-1β, IL-6, IL-8, TNF-α, GM-CSF) in primary human nasal epithelial cells and nasal polyp tissue compared to soluble galectin-10, demonstrating that the crystalline state determines the inflammatory potency of galectin-10. Recombinant protein engineering of crystalline vs. soluble Gal-10 states, cytokine/chemokine gene expression in primary cells and patient-derived nasal polyps Nano letters Medium 35274950
2023 Extracellular galectin-10 (released via EETosis) upregulates matrix metalloproteinase (MMP) production in normal human epidermal keratinocytes and dermal fibroblasts through activation of p38 MAPK, ERK, and JNK signaling pathways, potentially contributing to bullous pemphigoid blister formation. In vitro stimulation of NHEKs and NHDFs with recombinant galectin-10, real-time PCR, ELISA, Western blotting, signaling pathway inhibition assays Journal of dermatological science Medium 37640566
2001 Transcriptional regulation of galectin-10: a GC box (-44 to -50) is required for full promoter activity and for butyric acid-induced upregulation; Sp1 binds the GC box and Oct1 binds the Oct site (-255 to -261). AML3 binds the AML site and YY1 binds the Inr sequence, both functioning as silencers in the galectin-10 promoter. Promoter deletion analysis, supershift EMSA, transcription factor binding assays Life sciences Medium 11441910
2025 Galectin-10 silencing in human eosinophils reduces expression of IL-4, IL-5, IL-8, MBP, and TNF-α but not ECP, and decreases phosphorylation of p38 and p65 (NF-κB), indicating that galectin-10 promotes eosinophilic inflammation via the p38 MAPK/NF-κB pathway. siRNA knockdown in human eosinophils, Western blotting for p-p38 and p-p65, ELISA for cytokines and granule proteins Critical reviews in immunology Low 40921147
2025 Gal-10 crystal formation is driven by charge-charge attractions at protein-protein interaction interfaces and is sensitive to pH changes and charged residue substitutions at packing interfaces. Arginine-rich peptides (R9 and R12Y8) dissolve gal-10 crystals by disrupting inter-protein charge interactions; intratracheal administration of R12Y8 in a murine gal-10 crystal-induced lung inflammation model reduced proinflammatory cytokine release and inflammatory cell infiltration. In vitro crystal dissolution assays, in vivo murine intratracheal model, cytokine measurement ACS applied materials & interfaces Medium 39894983
2021 Recombinant galectin-10 stimulates prostaglandin E2 production in oral keratinocytes and gingival fibroblasts, and induces IL-8, MMP-9, and C-reactive protein secretion in gingival fibroblasts; conditioned media from rGal-10-treated fibroblasts induced osteoclast differentiation. Recombinant protein stimulation of primary cells, ELISA, osteoclast differentiation assay Molecular medicine reports Low 33300083

Source papers

Stage 0 corpus · 38 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Human CD4+CD25+ regulatory T cells: proteome analysis identifies galectin-10 as a novel marker essential for their anergy and suppressive function. Blood 162 17502455
2002 Charcot-Leyden crystal protein (galectin-10) is not a dual function galectin with lysophospholipase activity but binds a lysophospholipase inhibitor in a novel structural fashion. The Journal of biological chemistry 94 11834744
1999 Selective recognition of mannose by the human eosinophil Charcot-Leyden crystal protein (galectin-10): a crystallographic study at 1.8 A resolution. Biochemistry 74 10529229
2021 Eosinophil ETosis-Mediated Release of Galectin-10 in Eosinophilic Granulomatosis With Polyangiitis. Arthritis & rheumatology (Hoboken, N.J.) 71 33750029
2018 A Brief History of Charcot-Leyden Crystal Protein/Galectin-10 Research. Molecules (Basel, Switzerland) 57 30424011
2017 Regulatory Eosinophils Suppress T Cells Partly through Galectin-10. Journal of immunology (Baltimore, Md. : 1950) 56 28515279
2020 Galectin-10, the protein that forms Charcot-Leyden crystals, is not stored in granules but resides in the peripheral cytoplasm of human eosinophils. Journal of leukocyte biology 42 32108369
2020 Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis. The Journal of allergy and clinical immunology 38 31982451
2022 Galectin-10 as a Potential Biomarker for Eosinophilic Diseases. Biomolecules 37 36291593
2007 Galectin-10 mRNA is overexpressed in peripheral blood of aspirin-induced asthma. Allergy 37 17941953
2019 Charcot-Leyden crystal protein/galectin-10 is a surrogate biomarker of eosinophilic airway inflammation in asthma. Biomarkers in medicine 34 31157540
2021 Chronic rhinosinusitis with nasal polyposis (CRSwNP): the correlation between expression of Galectin-10 and Clinical-Cytological Grading (CCG). American journal of rhinology & allergy 33 34647485
2018 Galectin-10: a new structural type of prototype galectin dimer and effects on saccharide ligand binding. Glycobiology 31 29293962
2009 Galectin-10, eosinophils, and celiac disease. Annals of the New York Academy of Sciences 27 19758173
2020 Kinetic studies of galectin-10 release from eosinophils exposed to proliferating T cells. Clinical and experimental immunology 21 33080067
2021 Mepolizumab decreased the levels of serum galectin-10 and eosinophil cationic protein in asthma. Asia Pacific allergy 19 34386407
2019 Identification of key amino acid residues determining ligand binding specificity, homodimerization and cellular distribution of human galectin-10. Glycobiology 17 30239701
2001 Transcriptional regulation of galectin-10 (eosinophil Charcot-Leyden crystal protein): a GC box (-44 to -50) controls butyric acid induction of gene expression. Life sciences 17 11441910
2012 Galectin-10 is released in the nasal lavage fluid of patients with aspirin-sensitive respiratory disease. TheScientificWorldJournal 16 22654612
2024 Galectin-10 in serum extracellular vesicles reflects asthma pathophysiology. The Journal of allergy and clinical immunology 15 38551536
2020 Identification of galectin‑10 as a biomarker for periodontitis based on proteomic analysis of gingival crevicular fluid. Molecular medicine reports 11 33300083
2012 The mRNA level of the galectin-10 of Angiostrongylus cantonensis induced by reactive oxygen stress. Parasitology research 11 23224730
2023 Eosinophil-derived galectin-10 upregulates matrix metalloproteinase expression in bullous pemphigoid blisters. Journal of dermatological science 9 37640566
2022 Crystalline State Determines the Potency of Galectin-10 Protein Assembly to Induce Inflammation. Nano letters 9 35274950
2010 The mRNA level of Charcot-Leyden crystal protein/galectin-10 is a marker for CRTH2 activation in human whole blood in vitro. Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals 9 20858065
2023 Galectin-10 Expression in Placentas of Women with Gestational Diabetes. Current issues in molecular biology 8 37998731
2023 Extracellular distribution of galectin-10 in the esophageal mucosa of patients with eosinophilic esophagitis. Clinical and experimental immunology 5 36808213
2021 A potential contribution of decreased serum galectin-10 levels to systemic inflammation and pulmonary vascular involvement in systemic sclerosis. Experimental dermatology 3 33719171
2020 [Expression and pathological role of galectin-10 in different types of nasal polyps]. Zhonghua er bi yan hou tou jing wai ke za zhi = Chinese journal of otorhinolaryngology head and neck surgery 2 32911886
2025 Arginine-Rich Peptides Regulate the Pathogenic Galectin-10 Crystallization and Mitigate Crystallopathy-Associated Inflammation. ACS applied materials & interfaces 1 39894983
2025 C-BIOPRED severe asthma clinical phenotypes: link to complement and coagulation pathways and galectin 10. ERJ open research 1 40822235
2025 Galectin-10 Silencing Reduces Eosinophilic Inflammation in Chronic Rhinosinusitis with Nasal Polyps by Inhibiting the p38/MAPK/NF-κB Pathway. Critical reviews in immunology 1 40921147
2025 Plasma Galectin-4 and Charcot-Leyden Crystal Protein/Galectin-10 as Emerging Biomarkers of Metabolically Induced Inflammation in Patients with Psoriasis. International journal of molecular sciences 1 41226378
2024 Serum Galectin-10: A biomarker for persistent airflow limitation in adult asthmatics. The World Allergy Organization journal 1 39252790
2026 Salivary galectin-7, galectin-10, and MMP-9 levels in periodontally healthy, gingivitis, and periodontitis patients. Journal of periodontology 0 41553873
2026 Crystalline Insights into Nasal Mucosa Inflammation and Remodeling: Unveiling Role of Galectin-10. Biomolecules 0 41594617
2026 Structurally Resilient Peptide Assembly Regulates Pathogenic Galectin-10 Crystallization To Mitigate Crystallopathy Inflammation. Journal of the American Chemical Society 0 41808620
2025 Galectin-10 Characterization in Cleft Lip Palate - Affected Palatal Tissue. Acta medica Lituanica 0 40641544

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