title: Plasmacytoid dendritic cells orchestrate TLR7-mediated innate and adaptive immunity for the initiation of autoimmune inflammation.
abstract: Endosomal toll-like receptor (TLR)-mediated detection of viral nucleic acids (NAs) and production of type I interferon (IFN-I) are key elements of antiviral defense, while inappropriate recognition of self NAs with the induction of IFN-I responses is linked to autoimmunity such as psoriasis and systemic lupus erythematosus. Plasmacytoid dendritic cells (pDCs) are cells specialized in robust IFN-I secretion by the engagement of endosomal TLRs, and predominantly express sialic acid-binding Ig-like lectin (Siglec)-H. However, how pDCs control endosomal TLR-mediated immune responses that cause autoimmunity remains unclear. Here we show a critical role of pDCs in TLR7-mediated autoimmunity using gene-modified mice with impaired expression of Siglec-H and selective ablation of pDCs. pDCs were shown to be indispensable for the induction of systemic inflammation and effector T-cell responses triggered by TLR7 ligand. pDCs aggravated psoriasiform dermatitis mediated through the hyperproliferation of keratinocytes and enhanced dermal infiltration of granulocytes and γδ T cells. Furthermore, pDCs promoted the production of anti-self NA antibodies and glomerulonephritis in lupus-like disease by activating inflammatory monocytes. On the other hand, Siglec-H regulated the TLR7-mediated activation of pDCs. Thus, our findings reveal that pDCs provide an essential link between TLR7-mediated innate and adaptive immunity for the initiation of IFN-I-associated autoimmune inflammation.
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, SY 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, SY 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, SY 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, SY 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, SY 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: Division of Histochemistry and Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Narantsog
authors.initials: N
authors.lastname: Choijookhuu
authors.affiliation: Division of Histochemistry and Cell Biology, Department of Anatomy, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hishikawa
authors.affiliation: Division of Immunology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, SY 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: D056704:Adaptive Immunity; D000818:Animals; D001327:Autoimmune Diseases / Q000503:physiopathology*; D003713:Dendritic Cells / Q000276:immunology*; D003872:Dermatitis / Q000503:physiopathology; D004195:Disease Models, Animal; D005921:Glomerulonephritis / Q000503:physiopathology; D007113:Immunity, Innate; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D011565:Psoriasis / Q000503:physiopathology; D012867:Skin / Q000473:pathology; D051199:Toll-Like Receptor 7 / Q000378:metabolism*
chemical_list: D051199:Toll-Like Receptor 7