TIM1 is an endogenous ligand for LMIR5/CD300b: LMIR5 deficiency ameliorates mouse kidney ischemia/reperfusion injury

Yoshinori Yamanishi, Jiro Kitaura, Kumi Izawa, Ayako Kaitani, Yukiko Komeno, Masaki Nakamura, Satoshi Yamazaki, Yutaka Enomoto, Toshihiko Oki, Hisaya Akiba, Takaya Abe, Tadasuke Komori, Yoshihiro Morikawa, Hiroshi Kiyonari, Toshiyuki Takai, Ko Okumura, Toshio Kitamura

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

Leukocyte mono-immunoglobulin (Ig)-like receptor 5 (LMIR5)/CD300b is a DAP12-coupled activating receptor predominantly expressed in myeloid cells. The ligands for LMIR have not been reported. We have identified T cell Ig mucin 1 (TIM1) as a possible ligand for LMIR5 by retrovirus-mediated expression cloning. TIM1 interacted only with LMIR5 among the LMIR family, whereas LMIR5 interacted with TIM4 as well as TIM1. The Ig-like domain of LMIR5 bound to TIM1 in the vicinity of the phosphatidylserine (PS)-binding site within the Ig-like domain of TIM1. Unlike its binding to TIM1 or TIM4, LMIR5 failed to bind to PS. LMIR5 binding did not affect TIM1- or TIM4-mediated phagocytosis of apoptotic cells, and stimulation with TIM1 or TIM4 induced LMIR5-mediated activation of mast cells. Notably, LMIR5 deficiency suppressed TIM1-Fc-induced recruitment of neutrophils in the dorsal air pouch, and LMIR5 deficiency attenuated neutrophil accumulation in a model of ischemia/reperfusion injury in the kidneys in which TIM1 expression is up-regulated. In that model, LMIR5 deficiency resulted in ameliorated tubular necrosis and cast formation in the acute phase. Collectively, our results indicate that TIM1 is an endogenous ligand for LMIR5 and that the TIM1-LMIR5 interaction plays a physiological role in immune regulation by myeloid cells.

Original languageEnglish
Pages (from-to)1501-1511
Number of pages11
JournalJournal of Experimental Medicine
Volume207
Issue number7
DOIs
Publication statusPublished - 2010 Jul 5

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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