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

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

doi:10.1038/ncomms5710

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

Nat Commun. 2014 Aug 19:5:4710. doi: 10.1038/ncomms5710.

Authors

Affiliations

¹ 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [2] Department of Immunology, Fukushima Medical University, 1 Hikarigaoka, Fukushima, Fukushima 960-1295, Japan.
² 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [2] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [3] Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, 1500 East Medical Center Dr-4111 CCGC, Ann Arbor, Michigan 48109, USA.
³ Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁴ Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁵ 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [2] Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁶ 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [2] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
⁷ Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
⁸ 1] Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [2] Japan Science and Technology Agency, Core Research for Evolutional Science and Technology (CREST), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan [3] Life Science Center of Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.

Abstract

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 FcRγ chain-deficient mice. Lipopolysaccharide stimulation induces association of MAIR-II with FcRγ chain and Syk, leading to enhancement of VLA-4-mediated adhesion to VCAM-1. These results indicate that activation of MAIR-II/FcRγ 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cecum
Cell Adhesion / physiology
Cell Movement / physiology*
Disease Models, Animal
Female
Inflammation / etiology
Inflammation / pathology*
Inflammation / physiopathology
Integrin alpha4beta1 / physiology*
Ligation
Lipopolysaccharides / adverse effects
Male
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Monocytes / pathology*
Monocytes / physiology
Myeloid Differentiation Factor 88 / deficiency
Myeloid Differentiation Factor 88 / genetics
Myeloid Differentiation Factor 88 / physiology
Peritonitis / etiology
Peritonitis / pathology
Peritonitis / physiopathology
Receptors, Immunologic / deficiency
Receptors, Immunologic / genetics
Receptors, Immunologic / physiology*
Receptors, Polymeric Immunoglobulin / deficiency
Receptors, Polymeric Immunoglobulin / genetics
Receptors, Polymeric Immunoglobulin / physiology*
Signal Transduction / physiology
Toll-Like Receptor 4 / deficiency
Toll-Like Receptor 4 / genetics
Toll-Like Receptor 4 / physiology*

Substances

Integrin alpha4beta1
LMIR2 protein, mouse
Lipopolysaccharides
Myd88 protein, mouse
Myeloid Differentiation Factor 88
Receptors, Immunologic
Receptors, Polymeric Immunoglobulin
Tlr4 protein, mouse
Toll-Like Receptor 4
myeloid-associated Ig-like receptor , mouse