Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory receptor LMIR3

Kumi Izawa, Jiro Kitaura, Yoshinori Yamanishi, Takayuki Matsuoka, Toshihiko Oki, Fumi Shibata, Hidetoshi Kumagai, Hideaki Nakajima, Mari Maeda-Yamamoto, Jeffrey P. Hauchins, Victor L.J. Tybulewicz, Toshiyuki Takai, Toshio Kitamura

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Abstract

The leukocyte mono-Ig-like receptor (LMIR) belongs to a new family of paired immunoreceptors. In this study, we analyzed activating receptor LMIR4/CLM-5 as a counterpart of inhibitory receptor LMIR3/CLM-1. LMIR4 is expressed in myeloid cells, including granulocytes, macrophages, and mast cells, whereas LMIR3 is more broadly expressed. The association of LMIR4 with Fc receptor-γ among immunoreceptor tyrosine-based activation motif-bearing molecules was indispensable for LMIR4-mediated functions of bone marrow-derived mast cells, but dispensable for its surface expression. Cross-linking of LMIR4 led to Lyn- and Syk-dependent activation of bone marrow-derived mast cells, resulting in cytokine production and degranulation, whereas that of LMIR3 did not. The triggering of LMIR4 and TLR4 synergistically caused robust cytokine production in accordance with enhanced activation of ERK, whereas the co-ligation of LMIR4 and LMIR3 dramatically abrogated cytokine production. Notably, intraperitoneal administration of lipopolysaccharide strikingly up-regulated LMIR3 and down-regulated LMIR4, whereas that of granulocyte colony-stimulating factor upregulated both LMIR3 and LMIR4 in granulocytes. Cross-linking of LMIR4 in bone marrow granulocytes also resulted in their activation, which was enhanced by lipopolysaccharide. Collectively, these results suggest that the innate immune system is at least in part regulated by the qualitative and quantitative balance of the paired receptors LMIR3 and LMIR4.

Original languageEnglish
Pages (from-to)17997-18008
Number of pages12
JournalJournal of Biological Chemistry
Volume282
Issue number25
DOIs
Publication statusPublished - 2007 Jun 22

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Izawa, K., Kitaura, J., Yamanishi, Y., Matsuoka, T., Oki, T., Shibata, F., Kumagai, H., Nakajima, H., Maeda-Yamamoto, M., Hauchins, J. P., Tybulewicz, V. L. J., Takai, T., & Kitamura, T. (2007). Functional analysis of activating receptor LMIR4 as a counterpart of inhibitory receptor LMIR3. Journal of Biological Chemistry, 282(25), 17997-18008. https://doi.org/10.1074/jbc.M701100200