Pathological roles of a citrullinating enzyme PADI4 in rheumatoid arthritis

• Project/Area Number: 20390280
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: The University of Tokyo
• Principal Investigator: YAMAMOTO Kazuhiko The University of Tokyo, 医学部附属病院, 教授 (80191394)
• Co-Investigator(Kenkyū-buntansha): OKAMOTO Akiko 東京大学, 医学部附属病院, 助教 (40431861) ; HAGINO Noboru 東京大学, 医学部附属病院, 助教 (40466769)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000); Fiscal Year 2010: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2009: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2008: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
• Keywords: 免疫学 / ゲノム / 内科 / 遺伝子

Research Abstract

We have previously identified rheumatoid arthritis susceptibility polymorphisms in PADI4. This enzyme converts arginine residues to citrullines and anti-citrullinated peptide antibodies are the most specific autoantibodies in the disease. In order to understand the pathological mechanisms, we have generated and analyzed arthritis in PADI4 knock out mice.

Research Products

• [Journal Article] Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. (2011)
  • Author(s): Yukinori Okada, Tomomitsu Hirota, Yoichiro Kamatani, Atsushi Takahashi, Koichi Matsuda, Tatsuhiko Tsunoda, Toshihiro Tanaka, Michiaki Kubo, Yusuke Nakamura, Mayumi Tamari, Kazuhiko Yamamoto, Naoyuki Kamatani.
  • Journal Title: PLos Genetics. in press
  • Peer Reviewed
• [Journal Article] PADI4 polymorphism predisposes male smokers to rheumatoid arthritis. (2011)
  • Author(s): Kochi Y, Thabet MM, Suzuki A, Okada Y, Daha NA, Toes REM, Huizinga TWJ, Myouzen K, Kubo M, Yamada R, Nakamura Y, Yamamoto K.
  • Journal Title: Ann Rheum Dis 70 Pages: 512-515
  • Peer Reviewed
• [Journal Article] PAD14 polymorphism predisposes male smokers to rheumatoid arthrilis. (2011)
  • Author(s): Kochi Y, Thabet MM, Suzuki A, Okada Y, Daha NA, Toes REM, Huizinga TWJ, Myouzen K, Kubo M, Yamada R, Nakamura Y, Yamamoto K
  • Journal Title: Ann Rheum Dis Volume: 70 Pages: 512-515
  • Peer Reviewed
• [Journal Article] The family of IL-10 secreting CD4+T cells. (2010)
  • Author(s): Fujio K, Okamura T, Yamamoto K.
  • Journal Title: Advances in Immunology. 105 Pages: 99-130
• [Journal Article] The association of a nonsynonymous single-nucleotide polymorphism in TNFAIP3 with systemic lupus erythematosus and rheumatoid arthritis in the Japanese population. (2010)
  • Author(s): Shimane K, Kochi Y, Horita T, Ikari K, Amano H, Hirakata M, Okamoto A, Yamada R, Myouzen K, Suzuki A, Kubo M, Atsumi T, Koike T, Takasaki Y, Momohara S, Yamanaka H, Nakamura Y, Yamamoto K.
  • Journal Title: Arthritis Rheum. 62 Pages: 574-579
  • Peer Reviewed
• [Journal Article] Ethnogenetic heterogeneity of rheumatoid arthritis-implications for pathogenesis. (2010)
  • Author(s): Kochi Y, Suzuki A, Yamada R, Yamamoto K.
  • Journal Title: Nat Rev Rheumatol. 6 Pages: 290-295
  • Peer Reviewed
• [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. (2010)
  • Author(s): Kochi Y, Okada Y, Suzuki A, Ikari K, Terao C, Takahashi A, Yamazaki K, Hosono N, Myouzen K, Tsunoda T, Kamatani N, Furuichi T, Ikegawa S, Ohmura K, Mimori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamura Y, Yamamoto K.
  • Journal Title: Nat Genet. 42 Pages: 515-519
  • Peer Reviewed
• [Journal Article] Regulatory polymorphisms in EGR2 are associated with susceptibility to systemic lupus erythematosus. (2010)
  • Author(s): Myouzen K, Kochi Y, Shimane K, Fujio K, Okamura T, Okada Y, Suzuki A, Atsumi T, Ito S, Takada K, Mimori A, Ikegawa S, Yamada R, Nakamura Y, Yamamoto K.
  • Journal Title: Hum Mol Genet. 19 Pages: 2313-2320
  • Peer Reviewed
• [Journal Article] HLA-DRB1*0901 lowers anti-cyclic citrullinated peptide antibody levels in Japanese patients with rheumatoid arthritis. (2010)
  • Author(s): Okada Y, Suzuki A, Yamada R, Kochi Y, Shimane K, Myouzen K, Kubo M, Nakamura Y, Yamamoto K.
  • Journal Title: Ann Rheum Dis. 69 Pages: 1569-1570
  • Peer Reviewed
• [Journal Article] Common variations in PSMD3-CSF3 and PLCB4 are associated with neutrophil count. (2010)
  • Author(s): Okada Y, Kamatani Y, Takahashi A, Matsuda K, Hosono N, Ohmiya H, Daigo Y, Yamamoto K, Kubo M, Nakamura Y, Kamatani N.
  • Journal Title: Hum Mol Genet. 19 Pages: 2079-2085
  • Peer Reviewed
• [Journal Article] The family of IL-10 secreting CD4+ T cells. (2010)
  • Author(s): Fujio K, Okamura T, Yamamoto K
  • Journal Title: Advances in Immunology. Volume: 105 Pages: 99-130
  • Peer Reviewed
• [Journal Article] A regulatory variant in CCR6 is associated with rheumatoid arthritis susceptibility. (2010)
  • Author(s): Kochi Y, Okada Y, Suzuki A, Ikari K, Taco C, Takahashi A, Yamazeld K, Hosono N, Myouzen K, Tsunoda T, Kama tani N, Funrichi T, Ikegawa S, Ohmura K, Munori T, Matsuda F, Iwamoto T, Momohara S, Yamanaka H, Yamada R, Kubo M, Nakamum Y, Yamamoto K
  • Journal Title: Nat Genet Volume: 42 Pages: 515-519
  • Peer Reviewed
• [Journal Article] Contribution of a haplotype in the HLA region to anti-cyclic citrullinated peptide antibody positivity in rheumatoid arthritis, independently of HLA-DRB1. (2009)
  • Author(s): Okada Y, Yamada R, Suzuki A, Kochi Y, Shimane K, Myouzen K, Kubo M, Nakamura Y, Yamamoto K.
  • Journal Title: Arthritis Rheum. 60 Pages: 3582-3590
  • Peer Reviewed
• [Journal Article] Genetics of rheumatoid arthritis: underlying evidence of ethnic differences. (2009)
  • Author(s): Kochi Y, Suzuki A, Yamada R, Yamamoto K.
  • Journal Title: J Autoimmun. 32 Pages: 158-162
  • Peer Reviewed
• [Journal Article] FCRL3, an autoimmune susceptibility gene, has inhibitory potential on B-cell receptor-mediated signaling. (2009)
  • Author(s): Kochi Y, Myouzen K, Yamada R, Suzuki A, Kurosaki T, Nakamura Y, Yamamoto K.
  • Journal Title: J Immunol. 183 Pages: 5502-5510
  • Peer Reviewed
• [Journal Article] A single nucleotide polymorphism in the IRF5 promoter region is associated with susceptibility to rheumatoid arthritis in the Japanese population. (2009)
  • Author(s): Shimane K, Kochi Y, Yamada R, Okada Y, Suzuki A, Miyatake A, Kubo M, Nakamura Y, Yamamoto K.
  • Journal Title: Ann Rheum Dis. 68 Pages: 377-383
  • Peer Reviewed
• [Journal Article] CD4+CD25-LAG3+ regulatory T cells controlled by the transcription factor Egr-2. (2009)
  • Author(s): Okamura T, Fujio K, Shibuya M, Sumitomo S, Shoda H, Sakaguchi S, Yamamoto K.
  • Journal Title: Proc Natl Acad Sci USA. 106 Pages: 13974-13979
  • Peer Reviewed
• [Journal Article] SLC22A4 polymorphism and rheumatoid arthritis susceptibility : a replication study in a Japanese population and a metaanalysis. (2008)
  • Author(s): Okada Y, Mori M, Yamada R, Suzuki A, Kobayashi K, Kubo M, Nakamura Y, Yamamoto K.
  • Journal Title: J Rheumatol. 35 Pages: 1723-1728
  • Peer Reviewed
• [Journal Article] Splenic phagocytes promote responses to nucleosomes in (NZB x NZW) F1 mice. (2008)
  • Author(s): Okamoto A, Fujio K, van Rooijen N, Tsuno NH, Takahashi K, Tsurui H, Hirose S, Elkon KB, Yamamoto K.
  • Journal Title: J Immunol. 181 Pages: 5264-5271
  • Peer Reviewed
• [Journal Article] Functional SNPs in CD244 gene increase the risk of rheumatoid arthritis in a Japanese population. (2008)
  • Author(s): Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K.
  • Journal Title: Nat Genet. 40 Pages: 1224-1229
  • Peer Reviewed
• [Journal Article] Functional SNPs in CD244 gene increase the risk of rheumatoid arthritis in a Japanese population. (2008)
  • Author(s): Suzuki A, Yamada R, Kochi Y, Sawada T, Okada Y, Matsuda K, Kamatani Y, Mori M, Shimane K, Takahashi A, Tsunoda T, Miyatake A, Kubo M, Kamatani N, Nakamura Y, Yamamoto K
  • Journal Title: Nat Genet. 40 Pages: 1224-9