title: Crucial role of plasmacytoid dendritic cells in the development of acute colitis through the regulation of intestinal inflammation.
abstract: Disruption of intestinal homeostasis can lead to inflammatory bowel diseases endowed susceptibility genes and environmental factors affecting intestinal accumulation and activation of colitogenic phagocytes. Plasmacytoid dendritic cells (pDCs) are immune cells that had been proposed to control innate and adaptive immunity through the massive secretion of type I interferon (IFN-I). However, the contribution of pDCs to the progression of intestinal inflammation remains unclear. Here we show a critical role of pDCs in the initiation of acute colonic inflammation using T-cell-independent acute colitis model with a selective ablation of pDCs. Although pDCs accumulated in the inflamed colon upon mucosal injury, deficiency of pDCs attenuated the development of acute colitis independent of IFN-I signaling, accompanied by the diminished colonic production of proinflammatory cytokines. Furthermore, deficiency of pDCs impaired the mobilization of colitogenic phagocytes into the inflamed colon possibly mediated by the abrogated mucosal production of C-C chemokine receptor 2 ligand. Thus, our findings highlight a critical role of pDCs in the induction of the colonic inflammation that regulates the colonic accumulation of inflammatory phagocytes leading to the initiation and exacerbation of acute colitis, and they may serve a key role in controlling gut mucosal immune homeostasis.
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Arimura
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Takagi
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Uto
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fukaya
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Histochemistry and Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Choijookhuu
authors.affiliation: Division of Histochemistry and Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Hishikawa
authors.affiliation: Department of Oral and Maxillofacial Surgery, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan.|Japan Agency for Medical Research and Development (AMED), Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sato
mesh_terms: D000208:Acute Disease; D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D006801:Humans; D018928:Immunity, Mucosal; D007249:Inflammation / Q000276:immunology*; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010586:Phagocytes / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D054390:Receptors, CCR2 / Q000378:metabolism
chemical_list: C515335:Ccr2 protein, mouse; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D054390:Receptors, CCR2; D053633:Receptor, Interferon alpha-beta