Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration

作者：Totsuka Naoya; Kim Yun Gi; Kanemaru Kazumasa; Niizuma Kouta; Umemoto Eiji; Nagai Kei; Tahara Hanaoka Satoko; Nakahasi Oda Chigusa; Honda Shin ichiro; Miyasaka Masayuki; Shibuya Kazuko; Shibuya Akira^*

来源：Nature Communications, 2014, 5(1): 4710.

DOI：10.1038/ncomms5710

Inflammatory monocytes play an important role in host defense against infections. However, the regulatory mechanisms of transmigration into infected tissue are not yet completely understood. Here we show that mice deficient in MAIR-II (also called CLM-4 or LMIR2) are more susceptible to caecal ligation and puncture (CLP)-induced peritonitis than wild-type (WT) mice. Adoptive transfer of inflammatory monocytes from WT mice, but not from MAIR-II, TLR4 or MyD88-deficient mice, significantly improves survival of MAIR-II-deficient mice after CLP. Migration of inflammatory monocytes into the peritoneal cavity after CLP, which is dependent on VLA-4, is impaired in above mutant and FcR gamma chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcR gamma chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcR gamma chain by TLR4/MyD88-mediated signalling is essential for the transmigration of inflammatory monocytes from the blood to sites of infection mediated by VLA-4.

• 出版日期2014-8