{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSiglec‑14 is an activating member of the sialic acid‑binding immunoglobulin‑like lectin family that is expressed on neutrophils and monocytes and functions as a paired receptor with the inhibitory Siglec‑5. Sharing nearly identical glycan‑binding domains with Siglec‑5, Siglec‑14 instead associates with the adapter protein DAP12 to trigger pro‑inflammatory signaling pathways—including activation of p38 MAPK, AKT, and the inflammasome (with subsequent caspase‑1–mediated IL‑1β release)—in response to microbial ligands, such as those on group B Streptococcus and nontypeable Haemophilus influenzae. In addition, Siglec‑14 can recognize endogenous proteins like Hsp70 and vimentin, thereby influencing inflammatory cellular responses. An alternatively spliced, soluble isoform of Siglec‑14, generated via intron retention, appears to counteract these pro‑inflammatory signals by interfering with receptor interactions on the cell surface."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nGenetic variation in SIGLEC14, including complete gene deletions and fusion events with SIGLEC5, modulates the balance of immune activation and suppression in humans. Individuals lacking membrane‑bound Siglec‑14 tend to exhibit diminished pro‑inflammatory responses to bacterial infections, with consequences for disease outcomes in conditions such as chronic obstructive pulmonary disease and tuberculosis. Furthermore, genome‑wide studies have implicated SIGLEC14 in a range of contexts—from influencing plasma plasminogen levels and gene presence‑absence variations in gastric cancer, to modifying risk associations in Alzheimer’s disease via copy number variation and altered expression of paired receptors. These findings underscore the evolving recognition of Siglec‑14 as a critical modulator of host immunity and its potential impact on a broad spectrum of infectious and inflammatory pathologies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takashi Angata, Toshiyuki Hayakawa, Masahiro Yamanaka, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Immunomodulatory activity of extracellular Hsp70 mediated via paired receptors Siglec-5 and Siglec-14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.15252/embj.201591407"}], "href": "https://doi.org/10.15252/embj.201591407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26459514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26459514"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Takashi Angata, Takeo Ishii, Takashi Motegi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Siglec-14 reduces the risk of chronic obstructive pulmonary disease exacerbation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Life Sci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00018-013-1311-7"}], "href": "https://doi.org/10.1007/s00018-013-1311-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23519826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23519826"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chih-Ming Tsai, Angelica M Riestra, Syed Raza Ali, et al. 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