LMIR5 extracellular domain activates myeloid cells through Toll-like receptor 4

Vongsavanh Phongsisay, Ei'ichi Iizasa, Hiromitsu Hara, Sho Yamasaki

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    LMIR5/CD300b is an activating immunoglobulin-like receptor whose extracellular domain (LMIR5-Fc) is constitutively released from immune cells. The release of LMIR5-Fc is augmented upon stimulation with TLR agonists. LMIR5-Fc is reported to possess inflammatory activity and amplify LPS-induced lethal inflammation; however, its action mechanism has not been clarified. This study was aimed to identify receptors for LMIR5-Fc. Using NF-κB reporter cells in human monocytes THP1, LMIR5-Fc was solely found to trigger NF-κB activation among various signaling receptors examined. In addition, an injection of LMIR5-Fc into the mouse peritoneal resulted in a rapid production of inflammatory mediators and an amplification of LPS activity. Moreover, LMIR5-Fc-induced cytokine production was markedly reduced in TLR4-deficient mouse macrophages. Using TLR4 reporter cells, the LMIR5-Fc sample that contained a trace amount of endotoxin under the sensitivity of reporter cells triggered a potent NF-κB activation. Furthermore, the inflammatory activity of LMIR5-Fc was completely lost by heating but unchanged by polymyxin B pretreatment. Using TLR4 fusion protein, TLR4 was found to interact specifically with LMIR5-overexpressing cells. Therefore, LMIR5-Fc is new inflammatory mediator and endogenous ligand of TLR4. This study provides an insight into the positive feedback mechanism of inflammation through TLR4-LMIR5-Fc axis.

    Original languageEnglish
    Pages (from-to)169-177
    Number of pages9
    JournalMolecular Immunology
    Volume62
    Issue number1
    DOIs
    Publication statusPublished - Nov 2014

    All Science Journal Classification (ASJC) codes

    • Immunology
    • Molecular Biology

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