title: Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice.
abstract: Tyrosine kinase-2 (Tyk2) participates in the signaling pathways of multiple cytokines in innate and acquired immunity. In the present study, we investigated the in vivo involvement of Tyk2 in anti-type II collagen antibody-induced arthritis (CAIA) using Tyk2-deficient mice. Hind paws of wild-type mice showed massive swelling and erythema by arthritogenic antibody injection, whereas Tyk2-deficient mice did not show any signs of arthritis. Indeed, neither the infiltration of inflammatory cells nor the fibrillation of articular cartilages was observed in Tyk2-deficient mice. Tyk2 deficiency also reduced the production of T(h)1/T(h)17-related cytokines, the other proinflammatory cytokines and matrix metalloproteases, which are induced in the CAIA paw. Our results demonstrate a critical contribution of Tyk2 in the development of arthritis, and we propose that Tyk2 might be an important candidate for drug development.
authors.affiliation: Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ishizaki
authors.forename: Ryuta
authors.initials: R
authors.lastname: Muromoto
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Akimoto
authors.forename: Yuya
authors.initials: Y
authors.lastname: Ohshiro
authors.forename: Miki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Maeda
authors.forename: Kazuya
authors.initials: K
authors.lastname: Shimoda
authors.forename: Kenji
authors.initials: K
authors.lastname: Oritani
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsuda
mesh_terms: D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000235:genetics* / Q000276:immunology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000473:pathology; D002478:Cells, Cultured; D024043:Collagen Type II / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004890:Erythema; D005786:Gene Expression Regulation / Q000276:immunology; D007249:Inflammation; D007596:Joints / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D053634:TYK2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000906:Antibodies; D024043:Collagen Type II; D016207:Cytokines; D053634:TYK2 Kinase; C499356:Tyk2 protein, mouse