{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nLMIR5 (also known as CD300b) is a DAP12-coupled activating receptor predominantly expressed on myeloid cells that plays multifaceted roles in immune regulation. Early studies demonstrated that LMIR5 selectively interacts with T cell Ig mucin proteins such as TIM1 and TIM4, with binding occurring at specific Ig-like domains independent of phosphatidylserine recognition. Furthermore, activation of LMIR5 on mast cells through cross‐linking triggers proinflammatory responses via adaptor proteins; notably, mouse LMIR5 signals predominantly via DAP12 while human LMIR5 also involves a unique tyrosine residue (Y188), suggesting the existence of additional, unidentified adaptor pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn models of acute inflammation, LMIR5 has been implicated in sepsis and ischemia/reperfusion injury. Upon stimulation with TLR agonists, neutrophils release a soluble form of LMIR5 (sLMIR5) that amplifies LPS-induced inflammatory cytokine production. In fact, soluble LMIR5 acts as an endogenous ligand for TLR4, thereby creating a positive feedback loop that augments systemic inflammation and septic responses. The disruption of LMIR5 signaling notably decreases cytokine release and improves outcomes in murine models of LPS-induced sepsis, highlighting its critical role in inflammatory amplification."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, LMIR5 serves as a key recognition receptor in host responses to bacterial pathogens such as Campylobacter jejuni. The organism preferentially binds LMIR5, triggering DAP12-mediated signaling cascades that lead to the activation of transcription factors like NFAT. The engagement of LMIR5 by microbial components—including proteins and glycoconjugate complexes—suggests a broader involvement in pathogen recognition and subsequent immunopathology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2007-04-085787"}], "href": "https://doi.org/10.1182/blood-2007-04-085787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17928527"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17928527"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20090581"}], "href": "https://doi.org/10.1084/jem.20090581"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20566714"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20566714"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yoshinori Yamanishi, Mariko Takahashi, Kumi Izawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A soluble form of LMIR5/CD300b amplifies lipopolysaccharide-induced lethal inflammation in sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Immunol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4049/jimmunol.1201139"}], "href": "https://doi.org/10.4049/jimmunol.1201139"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22772446"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22772446"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Vongsavanh Phongsisay, Ei'ichi Iizasa, Hiromitsu Hara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "LMIR5 extracellular domain activates myeloid cells through toll-like receptor 4."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2014.06.012"}], "href": "https://doi.org/10.1016/j.molimm.2014.06.012"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25004110"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25004110"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Vongsavanh Phongsisay "}, {"type": "b", "children": [{"type": "t", "text": "Campylobacter jejuni targets immunoglobulin-like receptor LMIR5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2014.07.024"}], "href": "https://doi.org/10.1016/j.molimm.2014.07.024"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25172092"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25172092"}]}]}]}