title: Clec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity.
abstract: Dendritic cells (DCs) comprise several subsets that are critically involved in the initiation and regulation of immunity. Clec4A4/DC immunoreceptor 2 (DCIR2) is a C-type lectin receptor (CLR) exclusively expressed on CD8α(-) conventional DCs (cDCs). However, how Clec4A4 controls immune responses through regulation of the function of CD8α(-) cDCs remains unclear. Here we show that Clec4A4 is a regulatory receptor for the activation of CD8α(-) cDCs that impairs inflammation and T-cell immunity. Clec4a4(-/-)CD8α(-) cDCs show enhanced cytokine production and T-cell priming following Toll-like receptor (TLR)-mediated activation. Furthermore, Clec4a4(-/-) mice exhibit TLR-mediated hyperinflammation. On antigenic immunization, Clec4a4(-/-) mice show not only augmented T-cell responses but also progressive autoimmune pathogenesis. Conversely, Clec4a4(-/-) mice exhibit resistance to microbial infection, accompanied by enhanced T-cell responses against microbes. Thus, our findings highlight roles of Clec4A4 in regulation of the function of CD8α(-) cDCs for control of the magnitude and quality of immune response.
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Uto
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fukaya
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Arimura
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Department of Applied Biochemistry, Tokai University, 4-1-1 Kita-kaname, Hiratsuka-shi, 259-1292 Kanagawa, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Kojima
authors.affiliation: Centre d'Immunologie de Marseille-Luminy, Université de la Méditerrannée, Case 906, Institut National de la Santé et de la Recherche Médicale U631, and Centre National de la Recherche Scientifique UMR6102, Marseille 13288, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Malissen
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki, 889-1692, Japan.|Japan Science and Technology Agency, Precursory Research for Embryonic Science and Technology (PRESTO), 4-1-8 Hon-cho, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Katsuaki
authors.initials: K
authors.lastname: Sato
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000517:prevention & control; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D054884:Host-Pathogen Interactions / Q000276:immunology; D007111:Immunity, Cellular; D007249:Inflammation / Q000473:pathology*; D008024:Ligands; D008810:Mice, Inbred C57BL; D011134:Polysaccharides / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000737:chemistry / Q000378:metabolism*; D012190:Retroviridae / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism; D014161:Transduction, Genetic
chemical_list: D016827:CD8 Antigens; D016207:Cytokines; C000603984:DCIR2 protein, mouse; D000939:Epitopes; D008024:Ligands; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors