Role of Sox transcription factors in the onset of autoimmune diseases

2013 Fiscal Year Final Research Report

• Project/Area Number: 23591432
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: 膠原病・アレルギー・感染症内科学
• Research Institution: Chiba University
• Principal Investigator: SUTO Akira 千葉大学, 医学(系)研究科(研究院), 特任准教授 (50447306)
• Co-Investigator(Kenkyū-buntansha): SUZUKI Kotaro 千葉大学, 医学部附属病院, 講師 (90554634)
• Co-Investigator(Renkei-kenkyūsha): NAKAJIMA Hiroshi 千葉大学, 大学院医学研究院, 教授 (00322024)
• Project Period (FY): 2011 – 2013
• Keywords: Th17 / Sox5 / c-Maf

Research Abstract

Th17 cells play a pathogenic role in autoimmune diseases. It has been shown that IL-6- and/or IL-21-mediated activation of Stat3 is essential for the expression of RORgammat, which is a lineage-specifying transcription factor of Th17 cells. In this study, we find that Sox5 and c-Maf are induced in Th17 cells in a Stat3-dependent manner. Sox5 together with c-Maf induce Th17 cell differentiation as downstream effectors of Stat3 and as upstream inducers of RORgammat. In addition, we find that T cell-specific Sox5-deficient mice exhibit impaired Th17 cell differentiation and are resistant to experimental autoimmune encephalomyelitis and delayed-type hypersensitivity. Taken together, these results suggest that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORgammat as downstream targets of Stat3.

Research Products

• [Journal Article] IL-21-producing c-Maf-expressing CD4+ T cells induce effector CD8+ T cells and enhance autoimmune inflammation in scurfy mice (2014)
  • Author(s): Iwamoto T, Suto A, Tanaka S, Takatori H, Suzuki K, Iwamoto I, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: (巻不明)
  • DOI: 10.1002/art.38658
  • Peer Reviewed
• [Journal Article] AT-Rich-Interactive Domain-Containing Protein 5A Functions as a Negative Regulator of Retinoic Acid Receptor-Related Orphan Nuclear Receptorγt-Induced Th17 Cell Differentiation (2014)
  • Author(s): Saito Y, Kagami S, Sanayama Y, Ikeda K, Suto A, Kashiwakuma D, Furuta S, Iwamoto I, Nonaka K, Ohara O, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: 66 Pages: 1185-94
  • DOI: 10.1002/art.38324
  • Peer Reviewed
• [Journal Article] Th2-type inflammation instructs inflammatory dendritic cells to induce airway hyperreactivity (2014)
  • Author(s): Iwata A, Kawashima S, Kobayashi M, Okubo A, Kawashima H, Suto A, Hirose K, Nakayama T, Nakajima H
  • Journal Title: Int Immunol Volume: 26 Pages: 103-14
  • DOI: 10.1093/intimm/dxt047
  • Peer Reviewed
• [Journal Article] Tumor suppressor p53 inhibits systemic autoimmune diseases by inducing regulatory T cells (2013)
  • Author(s): Kawashima H, Takatori H, Suzuki K, Iwata A, Yokota M, Suto A, Minamino T, Hirose K, Nakajima H
  • Journal Title: J Immunol Volume: 191 Pages: 3614-23
  • DOI: 10.4049/jimmunol.1300509
  • Peer Reviewed
• [Journal Article] Alteration of circulating miRNAs in SSc : miR-30b regulates the expression of PDGF receptorβ (2013)
  • Author(s): Tanaka S, Suto A, Ikeda K, Sanayama Y, Nakagomi D, Iwamoto T, Suzuki K, Kambe N, Matsue H, Matsumura R, Kashiwakuma D, Iwamoto I, Nakajima H
  • Journal Title: Rheumatology (Oxford) Volume: 52 Pages: 1963-72
  • DOI: 10.1093/rheumatology/ket254
  • Peer Reviewed
• [Journal Article] Role of calcium ionophore A23187-induced activation of IkappaB kinase 2 in mast cells (2013)
  • Author(s): Hosokawa J, Suzuki K, Nakagomi D, Tamachi T, Takatori H, Suto A, Nakajima H
  • Journal Title: Int Arch Allergy Immunol Volume: 161 Pages: 37-43
  • DOI: 10.1159/000350357
  • Peer Reviewed
• [Journal Article] [18F]FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis (2013)
  • Author(s): Tanaka S, Ikeda K, Uchiyama K, Iwamoto T, Sanayama Y, Okubo A, Nakagomi D, Takahashi K, Yokota M, Suto A, Suzuki K, Nakajima H
  • Journal Title: Rheumatology (Oxford) Volume: 52 Pages: 1271-8
  • DOI: 10.1093/rheumatology/ket112
  • Peer Reviewed
• [Journal Article] B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells (2013)
  • Author(s): Kobayashi Y, Iwata A, Suzuki K, Suto A, Kawashima S, Saito Y, Owada T, Kobayashi M, Watanabe N, Nakajima H
  • Journal Title: Proc Natl Acad Sci U S A Volume: 110 Pages: 5121-6
  • DOI: 10.1073/pnas.1222093110
  • Peer Reviewed
• [Journal Article] Therapeutic potential of B and T lymphocyte attenuator expressed on CD8+ T cells for contact hypersensitivity (2013)
  • Author(s): Nakagomi D, Suzuki K, Hosokawa J, Kobayashi Y, Suto A, Takatori H, Watanabe N, Matsue H, Murphy TL, Murphy KM, Shimada S, Nakajima H
  • Journal Title: J Invest Dermatol Volume: 133 Pages: 702-11
  • DOI: 10.1038/jid.2012.396
  • Peer Reviewed
• [Journal Article] Bucillamine-induced yellow nail in Japanese patients with rheumatoid arthritis : two case reports and a review of 36 reported cases (2013)
  • Author(s): Nakagomi D, Ikeda K, Kawashima H, Kobayashi Y, Suto A, Nakajima H
  • Journal Title: Rheumatol Int Volume: 33 Pages: 793-7
  • DOI: 10.1007/s00296-011-2241-z
  • Peer Reviewed
• [Journal Article] Pre-dinner administration increases the efficacy of proton pump inhibitors on refractory GERD symptoms in connective tissue disease patients (2013)
  • Author(s): Iwata A, Ikeda K, Hirose K, Takatori H, Takahashi K, Sanayama Y, Tanaka S, Suto A, Nakajima H
  • Journal Title: Mod Rheumatol Volume: 23 Pages: 357-64
  • DOI: 10.1007/s10165-012-0662-5
  • Peer Reviewed
• [Journal Article] Subtilase cytotoxin enhances Escherichia coli survival in macrophages by suppression of nitric oxide production through the inhibition of NF-κB activation (2012)
  • Author(s): Tsutsuki H, Yahiro K, Suzuki K, Suto A, Ogura K, Nagasawa S, Ihara H, Shimizu T, Nakajima H, Moss J, Noda M
  • Journal Title: Infect Immun Volume: 80 Pages: 3939-51
  • DOI: 10.1128/IAI.00581-12
  • Peer Reviewed
• [Journal Article] Overexpression of RORγt under control of the CD2 promoter induces polyclonal plasmacytosis and autoantibody production in transgenic mice (2012)
  • Author(s): Yoh K, Morito N, Ojima M, Shibuya K, Yamashita Y, Morishima Y, Ishii Y, Kusakabe M, Nishikii H, Fujita A, Matsunaga E, Okamura M, Hamada M, Suto A, Nakajima H, Shibuya A, Yamagata K, Takahashi S
  • Journal Title: Eur J Immunol Volume: 42 Pages: 1999-2009
  • DOI: 10.1002/eji.201142250
  • Peer Reviewed
• [Journal Article] Lack of B and T lymphocyte attenuator exacerbates autoimmune disorders and induces Fas-independent liver injury in MRL-lpr/lpr mice (2011)
  • Author(s): Oya Y, Watanabe N, Kobayashi Y, Owada T, Oki M, Ikeda K, Suto A, Kagami S, Hirose K, Kishimoto T, Nakajima H
  • Journal Title: Int Immunol Volume: 23 Pages: 335-44
  • DOI: 10.1093/intimm/dxr017
  • Peer Reviewed
• [Presentation] [18F] FDG uptake in proximal muscles assessed by PET/CT reflects both global and local muscular inflammation and provides useful information in the management of patients with polymyositis/dermatomyositis (2013)
  • Author(s): S. Tanaka, K Ikeda, K. Uchiyama, T. Iwamoto, Y. Sanayama, A. Okubo, D. Nakagomi, K. Takahashi, M. Yokota, A. Suto, K. Suzuki, H. Nakajima
  • Organizer: EULAR Congress 2013
  • Place of Presentation: マドリッドスペイン
  • Year and Date: 20130612-15
• [Remarks]
  • URL: http://www.m.chiba-u.jp/class/allergy/research/index.html