IL-35 associate with the Th2 response and the differentiation of Tregs in type 1 AIP.

• Project/Area Number: 19K17476
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Kansai Medical University
• Principal Investigator: TANAKA Toshihiro 関西医科大学, 医学部, 研究医員 (70548700)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: IL-35 / 自己免疫性膵炎 / 制御性T細胞 / 自己免疫製膵炎 / IL-29

Outline of Research at the Start

IgG4-related pancreatitis(AIP)の病態には,制御性T細胞(Treg)が関与すると報告されているが,その増減に関与するメディエーターや詳細な関係性は未だ不明な点が多い.そこでTregに関与し,抑制的な働きをすると考えられるIL-35を中心としたサイトカインとAIPの病態との関連に注目した.ヒト検体で末梢血中のTregを用いて,IL-35との関係性の解析を進め,AIP膵組織でもその発現について確認を行い,病勢のバイオマーカー及び今後の新たな治療法となるかを検討する.

Outline of Final Research Achievements

IgG4-related disease (IgG4-RD) is a systemic inflammatory disease, which includes type 1 autoimmune pancreatitis (AIP). Interleukin-35 (IL-35) exhibits immunosuppressive effects in several autoimmune diseases.
However, the expression of IL-35 had not been reported so far in type 1 AIP. We evaluated the association
between IL-35 and several cytokines, which mediate the function of Tregs in type 1 AIP. This study identified elevated expression of plasma IL-35 and tissue IL-35 subunits in patients with type 1 AIP. This might lead to inflammation suppression via activated eTregs. IL-35 might be associated with this anti-inflammatory role, especially against the Th2 response through several cytokines and the differentiation of Tregs in type 1 AIP.

Academic Significance and Societal Importance of the Research Achievements

これまで詳細が不明瞭であった自己免疫性膵炎の病態において、その一端となるILー35とILー29の関与が明らかになった。抑制性の制御をするとのことで、今後治療への応用や、さらなる病態の解明につながる糸口となると考えられる。

Research Products

• [Journal Article] Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis (2020)
  • Author(s): Ito T, Tanaka T, Nakamaru K, Tomiyama T, Yamaguchi T, Ando Y, Ikeura T, Fukui T, Uchida K, Nishio A, Okazaki K.
  • Journal Title: J Gastroenterol . Volume: 55 Issue: 8 Pages: 789-799
  • DOI: 10.1007/s00535-020-01689-5
  • Peer Reviewed
• [Presentation] Interleukin-35 promotes the differentiation of regulatory T cells and suppresses Th2 response in IgG4-related type 1 autoimmune pancreatitis (2021)
  • Author(s): ◎Takashi Ito , Toshihiro Tanaka , Koh Nakamaru, Tsukasa Ikeura , Kazushige Uchida， Makoto Naganuma， Kazuichi Okazaki
  • Organizer: IgG42020+1 The 4th international Symposium on IgG4-Related Diseases The 13th Annual Meeting of Japanese Association of IgG4-Related Diseases
  • Int'l Joint Research