{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LAIR2 is a soluble homolog of the transmembrane inhibitory receptor LAIR‑1 that binds collagens with high affinity. Because its affinity for collagen exceeds that of LAIR‑1, LAIR2 functions as a natural decoy receptor, antagonizing LAIR‑1–mediated inhibitory signals and thereby modulating immune cell function."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " In several experimental models, recombinant LAIR2‐Fc proteins can efficiently block collagen interactions not only with LAIR‑1 but also with other collagen receptors, thereby relieving collagen‐induced inhibition of immune responses, interfering with platelet activation, and even modulating complement fixation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in antagonizing LAIR‑1, LAIR2 is emerging as an important immunomodulatory molecule in various disease settings. Altered expression levels and genetic variants of LAIR2 have been linked to autoimmune disorders (including autoimmune thyroid diseases and pemphigus foliaceus) and inflammatory conditions, where increased LAIR2 may counterbalance excessive inhibitory signals and serve as a potential biomarker of inflammation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": " In oncology, aberrant LAIR2 expression has been observed in tumor samples from renal cell carcinoma, cholangiocarcinoma, lung adenocarcinoma, and cutaneous T‐cell lymphoma, suggesting that LAIR2 may influence the tumor microenvironment by modulating immune cell infiltration and function; indeed, high LAIR2 levels often correlate with more aggressive disease or resistance to certain therapies."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "16"}]}, {"type": "t", "text": " \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of pregnancy, LAIR2 is expressed at the maternal–fetal interface. Its highly restricted expression in extravillous trophoblasts and in areas critical for spiral arteriole remodeling indicates that LAIR2 may regulate trophoblast invasion and vascular adaptation, with altered expression being associated with adverse outcomes such as preeclampsia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "20"}]}, {"type": "t", "text": " Moreover, studies in placental models further demonstrate that LAIR2 can modulate decidual natural killer cell function by interfering with LAIR‑1–collagen interactions, a mechanism that might contribute to the maintenance of immune tolerance during early pregnancy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "21"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, advances in detection methodologies – including the generation of monoclonal antibodies against LAIR2 – have improved our ability to study its distribution and function in diverse biological fluids such as plasma, urine, and synovial fluid. These technical developments not only support the utility of LAIR2 as a biomarker reflecting systemic inflammation but also underscore its potential as a target for novel immunotherapeutic strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "23"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, LAIR2 serves as a key immunomodulator by acting as a decoy receptor that interferes with collagen binding to LAIR‑1, thereby regulating inhibitory signaling across a variety of physiological and pathological settings, including immune homeostasis, tumor immunity, and placental development.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Myoungsun Son, Frances Santiago-Schwarz, Yousef Al-Abed, et al. 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