title: Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model.
abstract: Peptidyl arginine deiminase 4 (PAD4) is an enzyme that is involved in protein citrullination, and is a target for anti-citrullinated peptide antibodies (ACPAs) in rheumatoid arthritis (RA). Genetic polymorphisms in the PADI4 gene encoding PAD4 are associated with RA susceptibility. We herein analyzed the roles of PADI4 in inflammatory arthritis using a glucose-6-phosphate isomerase (GPI)-induced arthritis (GIA) model in Padi4 knockout (KO) mice. Arthritis severity, serum anti-GPI antibody titers, and IL-6 concentrations were significantly reduced in Padi4 KO mice. The frequency of Th17 cells was decreased in GPI-immunized Padi4 KO mice, whereas WT and Padi4-deficient naïve CD4(+) T cells displayed the same efficiencies for Th17 cell differentiation in vitro. In addition, the numbers of myeloid lineage cells were reduced with the increased expression of pro-apoptotic genes in GPI-immunized Padi4 KO mice. Furthermore, the survival of Padi4-deficient neutrophils was impaired in vitro. Our results suggest that PADI4 exacerbates arthritis with diverse immunological modifications.
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors: Yu
authors: Y
authors: Seri
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors: Hirofumi
authors: H
authors: Shoda
authors: Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
authors: Akari
authors: A
authors: Suzuki
authors: Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, Tsukuba University, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Isao
authors: I
authors: Matsumoto
authors: Division of Clinical Immunology, Major of Advanced Biomedical Applications, Graduate School of Comprehensive Human Sciences, Tsukuba University, Tsukuba, Ibaraki, 305-8575, Japan.
authors: Takayuki
authors: T
authors: Sumida
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.
authors: Keishi
authors: K
authors: Fujio
authors: Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Bunkyo-ku, Tokyo, 113-8655, Japan.|Laboratory for Rheumatic Diseases, SNP Research Center, The Institute of Physical and Chemical Research (RIKEN), 1-7-22 Suehirocho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan.
authors: Kazuhiko
authors: K
authors: Yamamoto
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology*; D001402:B-Lymphocytes / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000276:immunology; D006801:Humans; D006867:Hydrolases / Q000172:deficiency* / Q000378:metabolism; D007114:Immunization; D015850:Interleukin-6 / Q000097:blood; D018655:Lymphocyte Count; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology; D009504:Neutrophils / Q000166:cytology; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; D012720:Severity of Illness Index; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000906:Antibodies; D039481:CD11b Antigen; D015850:Interleukin-6; D006867:Hydrolases; C000629235:PADI4 protein, human; D000080002:Protein-Arginine Deiminase Type 4; D000076342:Protein-Arginine Deiminases; C552151:peptidylarginine deiminase 4, mouse; D005956:Glucose-6-Phosphate Isomerase