Analysis of mouse LMIR5/CLM-7 as an activating receptor: Differential regulation of LMIR5/CLM-7 in mouse versus human cells

Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Takayuki Matsuoka, Toshihiko Oki, Yang Lu, Fumi Shibata, Satoshi Yamazaki, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Victor L J Tybulewicz, Toshiyuki Takai, Toshio Kitamura

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

We have analyzed leukocyte mono-Ig-like receptor 5 (LMIR5) as an activating receptor among paired LMIRs. Mouse LMIR5 (mLMIR5) is expressed in myeloid cells such as mast cells, granulocytes, macrophages, and dendritic cells. Cross-linking of transduced mLMIR5 in bone marrow-derived mast cells (BMMCs) caused activation events, including cytokine production, cell survival, degranulation, and adhesion to the extracellular matrix. mLMIR5 associated with DAP12 and to a lesser extent with DAP10, and mLMIR5-mediated functions of BMMCs were strongly inhibited by DAP12 deficiency. Importantly, cross-linking of endogenous mLMIR5 induced Syk-dependent activation of fetal liver-derived mast cells. Unlike mLMIR5, cross-linking of human LMIR5 (hLMIR5) induced cytokine production of BMMCs even in the absence of both DAP12 and DAP10, suggesting the existence of unidentified adaptors. Interestingly, hLMIR5 possessed a tyrosine residue (Y188) in the cytoplasmic region. Signaling via Y188 phosphorylation played a predominant role in hLMIR5-mediated cytokine production in DAP12-deficient, but not wildtype BMMCs. In addition, experiments using DAP10/DAP12 double-deficient BMMCs suggested the existence of Y188 phoshorylation-dependent and -independent signals from unidentified adaptors. Collectively, although both mouse and human LMIR5 play activatory roles in innate immunity cells, the functions of LMIR5 were differentially regulated in mouse versus human cells.

Original languageEnglish (US)
Pages (from-to)688-698
Number of pages11
JournalBlood
Volume111
Issue number2
DOIs
StatePublished - Jan 15 2008

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Yamanishi, Y., Kitaura, J., Izawa, K., Matsuoka, T., Oki, T., Lu, Y., Shibata, F., Yamazaki, S., Kumagai, H., Nakajima, H., Maeda-Yamamoto, M., Tybulewicz, V. L. J., Takai, T., & Kitamura, T. (2008). Analysis of mouse LMIR5/CLM-7 as an activating receptor: Differential regulation of LMIR5/CLM-7 in mouse versus human cells. Blood, 111(2), 688-698. https://doi.org/10.1182/blood-2007-04-085787