title: Toll-like receptor 4 and MAIR-II/CLM-4/LMIR2 immunoreceptor regulate VLA-4-mediated inflammatory monocyte migration.
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.
authors.affiliation: 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.
authors.forename: Naoya
authors.initials: N
authors.lastname: Totsuka
authors.affiliation: 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.
authors.forename: Yun-Gi
authors.initials: YG
authors.lastname: Kim
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Kanemaru
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kouta
authors.initials: K
authors.lastname: Niizuma
authors.affiliation: Laboratory of Immune Regulation, Department of Microbiology and Immunology, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Umemoto
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Nagai
authors.affiliation: 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.
authors.forename: Satoko
authors.initials: S
authors.lastname: Tahara-Hanaoka
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Chigusa
authors.initials: C
authors.lastname: Nakahasi-Oda
authors.affiliation: 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.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Honda
authors.affiliation: Interdisciplinary Program for Biomedical Sciences, Institute for Academic Initiatives, Osaka University, 1-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Miyasaka
authors.affiliation: Department of Immunology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Shibuya
authors.affiliation: 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.
authors.forename: Akira
authors.initials: A
authors.lastname: Shibuya
mesh_terms: D000818:Animals; D002432:Cecum; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D039041:Integrin alpha4beta1 / Q000502:physiology*; D008026:Ligation; D008070:Lipopolysaccharides / Q000009:adverse effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology* / Q000502:physiology; D053594:Myeloid Differentiation Factor 88 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D010538:Peritonitis / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D019056:Receptors, Polymeric Immunoglobulin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D039041:Integrin alpha4beta1; C476772:LMIR2 protein, mouse; D008070:Lipopolysaccharides; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011971:Receptors, Immunologic; D019056:Receptors, Polymeric Immunoglobulin; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C517261:myeloid-associated Ig-like receptor, mouse