{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSIGLEC5 is a sialic acid–binding immunoglobulin‐like receptor predominantly expressed on myeloid cells that acts as an inhibitory checkpoint in innate and adaptive immunity. Engagement of SIGLEC5 by its ligands triggers immunoreceptor tyrosine‐based inhibitory motifs in its cytoplasmic tail, recruiting phosphatases such as SHP‐1 and SHP‐2 to attenuate cellular activation. Several studies have documented that pathogens such as Group B Streptococcus exploit SIGLEC5 through noncanonical protein–protein interactions (via the bacterial β‐protein) to suppress phagocyte responses, an effect balanced in part by the presence of the activating paired receptor SIGLEC14. Moreover, binding of endogenous molecules (e.g., extracellular Hsp70) to SIGLEC5 delivers anti‐inflammatory signals, and increased SIGLEC5 expression on T cells can modulate lymphocyte activation and survival."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and biochemical investigations have elucidated the specificity of SIGLEC5 for sialylated glycans. Crystallographic studies reveal a conserved sialic acid binding pocket, involving critical residues (e.g., an essential arginine), while biochemical assays further outline its promiscuous binding to various glycan structures. In addition, SIGLEC5 participates in the uptake of immunoglobulin A (SIgA) via M cell–mediated transcytosis, and its interactions with glycoproteins like PSGL1 regulate leukocyte adhesion and rolling. Notably, SIGLEC5-mediated responses to acute-phase proteins (for example, alpha1-acid glycoprotein) depend on its sialic acid recognition, and recent work has also implicated SIGLEC5 in the endocytic clearance of glycosylated plasma proteins such as ADAMTS13."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "15"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in modulating immune cell activation and pathogen evasion, altered expression or genetic variation in SIGLEC5 has important clinical implications. Elevated expression on malignant cells—as seen in certain leukemias—and on activated T cells has spurred interest in its potential as a therapeutic target and biomarker in cancer. In autoimmune and inflammatory conditions, including primary Sjögren’s syndrome, periodontitis, and sepsis, aberrant SIGLEC5 levels correlate with disease severity. Plasma levels of SIGLEC5 have furthermore been associated with critical complications in type 2 diabetes mellitus and may contribute to gene × gene interaction effects underlying susceptibility to chronic inflammatory diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "16", "end_ref": "25"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Syed Raza Ali, Jerry J Fong, Aaron F Carlin, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Siglec-5 (CD170) can mediate inhibitory signaling in the absence of immunoreceptor tyrosine-based inhibitory motif phosphorylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502041200"}], "href": "https://doi.org/10.1074/jbc.M502041200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15769739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15769739"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jerry J Fong, Karthik Sreedhara, Liwen Deng, et al. 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