title: Negative regulation of DSS-induced experimental colitis by PILRα.
abstract: Inflammatory bowel disease is thought to be a complex multifactorial disease, in which an increased inflammatory response plays an important role. Paired immunoglobulin-like type 2 receptor α (PILRα), well conserved in almost all mammals, is an inhibitory receptor containing immunoreceptor tyrosine-based inhibitory motifs in the cytoplasmic domain. PILRα is mainly expressed on myeloid cells and plays an important role in the regulation of inflammation. In the present study, we investigated the function of PILRα in inflammatory bowel disease using PILRα-deficient mice. When mice were orally administered dextran sulfate sodium (DSS), colonic mucosal injury and inflammation were significantly exacerbated in DSS-treated PILRα-deficient mice compared with wild-type (WT) mice. Flow cytometric analysis revealed that neutrophil and macrophage cell numbers were higher in the colons of DSS-treated PILRα-deficient mice than in those of WT mice. Blockade of CXCR2 expressed on neutrophils using a CXCR2 inhibitor decreased the severity of colitis observed in PILRα-deficient mice. These results suggest that PILRα negatively regulates inflammatory colitis by regulating the infiltration of inflammatory cells such as neutrophils and macrophages.
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Kishida
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Kohyama
authors.affiliation: Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kurashima
authors.forename: Yuta
authors.initials: Y
authors.lastname: Kogure
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan Present address: Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Kouyuki
authors.initials: K
authors.lastname: Hirayasu
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Suenaga
authors.affiliation: Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyono
authors.affiliation: Division of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, The Institute of Medical Science, The University of Tokyo, Minato-ku, Tokyo 108-8639, Japan Laboratory of Vaccine Materials, National Institute of Biomedical Innovation, Ibaraki, Osaka 567-0085, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kunisawa
authors.affiliation: Laboratory of Immunochemistry, WPI Immunology Frontier Research Center, Osaka University, Suita, Osaka 565-0871, Japan Department of Immunochemistry, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan arase@biken.osaka-u.ac.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Arase
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000473:pathology / Q000502:physiology*; D016264:Dextran Sulfate / Q000008:administration & dosage; D018450:Disease Progression; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D023421:Models, Animal; D009504:Neutrophils / Q000502:physiology*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000037:antagonists & inhibitors
chemical_list: C548037:PILRalpha protein, mouse; D011971:Receptors, Immunologic; D023063:Receptors, Interleukin-8B; D016264:Dextran Sulfate
keywords: colitis; immune regulation; inflammation; inhibitory receptor