{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CLEC4A (also known as dendritic cell immunoreceptor, DCIR) is a C‐type lectin receptor expressed by several antigen‐presenting cells—including plasmacytoid and myeloid dendritic cells, monocytes, and B cells—that plays diverse roles in the regulation of immune responses. It functions as an antigen‐uptake receptor by mediating clathrin‐dependent internalization and routing of captured antigen into endo–lysosomal compartments to facilitate cross‐presentation to T cells."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Moreover, the receptor contains an immunoreceptor tyrosine‐based inhibitory motif (ITIM) that enables it to modulate Toll‐like receptor–mediated signals; engagement of CLEC4A can dampen type I interferon and certain proinflammatory cytokine responses, thereby acting as a negative regulator of immune activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " In addition, CLEC4A participates in pathogen recognition; for example, it can directly bind HIV‐1 components, facilitating both virus capture and subsequent transmission, and triggering specific intracellular signaling pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Engagement of CLEC4A by glycosylated ligands—such as sialylated immunoglobulin G (IVIg)—can also induce tolerogenic responses, including the expansion of regulatory T cells and attenuation of inflammatory responses, which has potential therapeutic implications."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, genetic studies have linked polymorphisms within the CLEC4A gene to an increased susceptibility to autoimmune conditions, notably in subtypes of rheumatoid arthritis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Finally, evidence from infectious disease models such as cerebral malaria suggests that CLEC4A plays a role in modulating inflammation and immune cell recruitment, thereby influencing disease severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Overall, CLEC4A/DCIR emerges as a multifunctional receptor that bridges antigen capture and presentation with the fine‐tuning of innate and adaptive immune responses, thereby contributing to both host defense and immunoregulatory processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Friederike Meyer-Wentrup, Daniel Benitez-Ribas, Paul J Tacken, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Targeting DCIR on human plasmacytoid dendritic cells results in antigen presentation and inhibits IFN-alpha production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-03-081398"}], "href": "https://doi.org/10.1182/blood-2007-03-081398"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18258799"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18258799"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Eynav Klechevsky, Anne-Laure Flamar, Yanying Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cross-priming CD8+ T cells by targeting antigens to human dendritic cells through DCIR."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-01-264960"}], "href": "https://doi.org/10.1182/blood-2010-01-264960"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20530286"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20530286"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Karien Bloem, Ilona M Vuist, Meike van den Berk, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCIR interacts with ligands from both endogenous and pathogenic origin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Immunol Lett (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.imlet.2013.11.007"}], "href": "https://doi.org/10.1016/j.imlet.2013.11.007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24239607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24239607"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Friederike Meyer-Wentrup, Alessandra Cambi, Ben Joosten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCIR is endocytosed into human dendritic cells and inhibits TLR8-mediated cytokine production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Leukoc Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1189/jlb.0608352"}], "href": "https://doi.org/10.1189/jlb.0608352"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19028959"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19028959"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Alexandra A Lambert, Frédéric Barabé, Caroline Gilbert, et al. "}, {"type": "b", "children": [{"type": "t", "text": "DCIR-mediated enhancement of HIV-1 infection requires the ITIM-associated signal transduction pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-01-331363"}], "href": "https://doi.org/10.1182/blood-2011-01-331363"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21536857"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21536857"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alexandra A Lambert, Caroline Gilbert, Manon Richard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C-type lectin surface receptor DCIR acts as a new attachment factor for HIV-1 in dendritic cells and contributes to trans- and cis-infection pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2008-01-136473"}], "href": "https://doi.org/10.1182/blood-2008-01-136473"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18541725"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18541725"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Amir H Massoud, Madelaine Yona, Di Xue, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Dendritic cell immunoreceptor: a novel receptor for intravenous immunoglobulin mediates induction of regulatory T cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Allergy Clin Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jaci.2013.09.029"}], "href": "https://doi.org/10.1016/j.jaci.2013.09.029"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24210883"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24210883"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jianping Guo, Xinyu Wu, Chun Lai Too, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A replication study confirms the association of dendritic cell immunoreceptor (DCIR) polymorphisms with ACPA - negative RA in a large Asian cohort."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0041228"}], "href": "https://doi.org/10.1371/journal.pone.0041228"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22829930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22829930"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Maha Maglinao, Robert Klopfleisch, Peter H Seeberger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The C-type lectin receptor DCIR is crucial for the development of experimental cerebral malaria."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1203451"}], "href": "https://doi.org/10.4049/jimmunol.1203451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23918990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23918990"}]}]}]}