Analysis of in vivo functions of LMIR3/4/5

点击翻译按钮获取中文摘要

In the present study, we have clarified the physiological functions of LMIR3/4/5. Co-engagement of FcεRI and LMIR3 impaired cytokine production in bone marrow-derived mast cells (BMMCs) induced by FcεRI crosslinking alone, demonstrating that LMIR3 is an inhibitory receptor. On the other hand, LMIR3 has a unique receptor to associate with FcRγ and thereby functions as an activating receptor in concert with TLR4 stimulation. We have identified T cell Ig mucin I (TIM1) by retrovirus-mediated expression cloning. 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, TIM1-LMIR5 interaction plays a physiological role in immune regulation by myeloid cells.