Role of Sox molecules in the development of autoimmune diseases

• Project/Area Number: 26461461
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Chiba University
• Principal Investigator: Suto Akira 千葉大学, 大学院医学研究院, 特任准教授 (50447306)
• Co-Investigator(Kenkyū-buntansha): 鈴木 浩太郎 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): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: Sox12 / 自己免疫性腸炎 / Sox5 / 腸炎 / SoxC / Treg / 自己免疫疾患

Outline of Final Research Achievements

We have previously shown that Sox5 and c-Maf cooperatively induce Th17 cell differentiation via the induction of RORγt as downstream targets of Stat3. However, the role of other Sox family molecules in the development of autoimmune diseases was still largely unknown. Here, we show that the expression of Sox12, a member of SoxC family, is significantly induced in Treg cells under inflammatory conditions. Although Sox12 is not required for the development of nTreg cells, Sox12 is involved in the development of pTreg cells under inflammatory conditions in adoptive transfer colitis models. Moreover, we found that enforced expression of Sox12 is sufficient to promote Foxp3 expression in CD4+ T cells even in the absence of TGF-β or IL-2 and that Sox12 binds to Foxp3 promoter and drives its transcription.

Research Products

• [Journal Article] IκBNS induces Muc5ac expression in epithelial cells and causes airway hyperresponsiveness in murine asthma models (2017)
  • Author(s): Yokota M, Tamachi T, Yokoyama Y, Maezawa Y, Takatori T, Suto A, Suzuki K, Hirose K, Takeda K, Nakajima H
  • Journal Title: Allergy Volume: 印刷中 Issue: 7 Pages: 13079-13079
  • DOI: 10.1111/all.13079
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] T-bet inhibits innate lymphoid cell-mediated eosinophilic airway inflammation by suppressing IL-9 production (2017)
  • Author(s): Matsuki A, Takatori T, Makita S, Yokota M, Tamachi T, Suto A, Suzuki K, Hirose K, Nakajima H
  • Journal Title: J. Allergy Clin. Immunol Volume: 印刷中 Issue: 4 Pages: 31023-31025
  • DOI: 10.1016/j.jaci.2016.08.022
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] IkBNS enhances follicular helper T-cell differentiation and function downstream of ASCL2. (2016)
  • Author(s): Hosokawa J, Suzuki K, Meguro K, Tanaka S, Maezawa Y, Suto A, Fujimura L, Sakamoto A, Clevers H, Ohara O, Nakajima H.
  • Journal Title: J Allergy Clin Immunol. Volume: S0091-6749 Issue: 1 Pages: 32476-32479
  • DOI: 10.1016/j.jaci.2016.10.047
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] SOCS3 expressed in M2 macrophages attenuates contact hypersensitivity by suppressing MMP12 production (2016)
  • Author(s): Meguro K, Nakagomi D, Suzuki K, Hosokawa J, Fukuta T, Yokota M, Maezawa Y, Suto A, Nakajima H
  • Journal Title: J Invest Dermatol Volume: in press Issue: 3 Pages: 649-57
  • DOI: 10.1016/j.jid.2015.12.010
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Sox5 and Th17 cell differentiation. (2015)
  • Author(s): Suto A, Tanaka S, Nakajima H.
  • Journal Title: Oncotarget. Volume: 6 Pages: 19952-3
• [Journal Article] Roles of B Cell Leukemia/Lymphoma 3 in the development of T follicular helper cells and the pathogenesis of rheumatoid arthritis. (2015)
  • Author(s): Meguro, K., Suzuki, K., Hosokawa, J., Sanayama, Y., Tanaka, S., Furuta, S., Ikeda, K., Takatori, H, Suto, A., Sakamoto, A., Ohara, O., Nakajima, H.
  • Journal Title: Arthritis & Rheumatology Volume: 67 Issue: 10 Pages: 2651-60
  • DOI: 10.1002/art.39266
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Helios enhances regulatory T cell function in cooperation with Foxp3 (2015)
  • Author(s): Takatori H, Kawashima H, Matsuki A, Meguro K, Tanaka S, Iwamoto T, Sanayama Y, Nishikawa N, Tamachi T, Ikeda K, Suto A, Suzuki K, Kagami S, Hirose K, Kubo M, Hori S, Nakajima H
  • Journal Title: Arthritis Rheumatol Volume: 67 Issue: 6 Pages: 1491-502
  • DOI: 10.1002/art.39091
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] MMP12 is produced by M2 monocytes-macrophages and plays important roles in the development of contact hypersensitivity (2015)
  • Author(s): Nakagomi D, Suzuki K, Meguro K, Hosokawa J, Tamachi T, Takatori H, Suto A, Matsue H, Ohara O, Nakayama T, Shimada S, Nakajima H
  • Journal Title: J Allergy Clin Immunol Volume: 135 Issue: 5 Pages: 1397-400
  • DOI: 10.1016/j.jaci.2014.10.055
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Helios enhances regulatory T cell function in cooperation with Foxp3. (2015)
  • Author(s): Takatori H, Kawashima H, Matsuki A, Meguro K, Tanaka S, Iwamoto T, Sanayama Y, Nishikawa N, Tamachi T, Ikeda K, Suto A, Suzuki K, Kagami SI, Hirose K, Kubo M, Hori S, Nakajima H.
  • Journal Title: Arthritis Rheumatol. Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Sox5 and c-Maf cooperatively induce Th17 cell differentiation via ROR gamma t induction as downstream targets of Stat3 (2014)
  • Author(s): Tanaka S, Suto A, Iwamoto T, Kashiwakuma D, Kagami S, Suzuki K, Takatori H, Tamachi T, Hirose K, Onodera A, Suzuki J, Ohara O, Yamashita M, Nakayama T, Nakajima H
  • Journal Title: J Exp Med Volume: 211 Issue: 9 Pages: 1857-1874
  • DOI: 10.1084/jem.20130791
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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) Issue: 8 Pages: 2079-2090
  • DOI: 10.1002/art.38658
  • Peer Reviewed
• [Journal Article] Matrix metalloproteinase 12 is produced by M2 macrophages and plays important roles in the development of contact hypersensitivity. (2014)
  • Author(s): Nakagomi D, Suzuki K, Meguro K, Hosokawa J, Tamachi T, Takatori H, Suto A, Matsue H, Ohara O, Nakayama T, Shimada S, Nakajima H.
  • Journal Title: J Allergy Clin Immunol. Volume: 未定
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] AT-rich interactive domain-containing protein 5a functions as a negative regulator of RORγt-induced Th17 cell differentiation. (2014)
  • Author(s): Saito Y, Kagami SI, Sanayama Y, Ikeda K, Suto A, Kashiwakuma D, Furuta S, Iwamoto I, Nonaka K, Ohara O, Nakajima H.
  • Journal Title: Arthritis and Rheumatology Volume: 印刷中 Issue: 5 Pages: 1185-94
  • DOI: 10.1002/art.38324
  • Peer Reviewed
• [Presentation] Role of Sox5 in the development of Th17 cells (2014)
  • Author(s): Suto A
  • Organizer: The 2nd Symposium of International Immunological Memory and Vaccine Forum (IIMVF)
  • Place of Presentation: La Jolla Institute for Allergy & Immunology (La Jolla, California, USA)
  • Year and Date: 2014-08-25 – 2014-08-26
• [Remarks] 千葉大学大学院医学研究院 アレルギー・臨床免疫学
  • URL: http://www.m.chiba-u.jp/class/allergy/research/index.html
• [Remarks] 千葉大学大学院医学研究院 アレルギー・臨床免疫学 研究業績
  • URL: http://www.m.chiba-u.jp/class/allergy/research/index.html