Glucocorticoids enhance the differentiation and function of Th17 cells and cause colitis

• Project/Area Number: 18K15184
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: Kyoto University
• Principal Investigator: Shimba Akihiro 京都大学, 医学研究科, 助教 (30812242)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: グルココルチコイド / ストレス / Th17細胞 / 大腸炎 / ILC3 / ステロイドホルモン / ＴＨ17 / 炎症性腸疾患

Outline of Final Research Achievements

Glucocorticoids are a class of steroid hormone produced from adrenal cortex and have the strong immunosuppressive effects and used for clinical treatment on inflammatory diseases. Interleukin-17-producing helper T cells (Th17 cells) are critical to exacerbate inflammatory diseases but the effects of glucocorticoids on Th17 cells remain unclear. We found that glucocorticoids enhanced the differentiation and function of Th17 cells via promoting glycolysis and glycolysis-associated gene expression in vitro and in inflammatory disease mouse models such as experimental autoimmune encephalomyelitis (EAE) and colitis. Furthermore, stress-induced glucocortioids also enhanced Th17 cel geneeration in duodenum to promote neutrophil infiltration and inflammation.

Academic Significance and Societal Importance of the Research Achievements

免疫抑制剤として炎症性疾患の治療に用いられているグルココルチコイドが病原性のあるTh17細胞の機能をむしろ促進する働きを持つという知見は、他の研究とは一線を画する。Th17細胞がグルココルチコイド耐性を持つことやグルココルチコイドにより機能が促進されることで、喘息や大腸炎の病態の再燃化や慢性化に繋がる機構が考察できることが期待される。また、免疫抑制効果のあるグルココルチコイドが産生されるストレス状況下において、炎症性疾患が惹起される機構について、グルココルチコイドがTh17細胞の発生を促進するという機構により、この疑問が解決されることが期待される。

Research Products

• [Journal Article] Chronic circadian misalignment accelerates immune senescence and abbreviates lifespan in mice (2020)
  • Author(s): Inokawa Hitoshi, Umemura Yasuhiro, Shimba Akihiro, Kawakami Eiryo, Koike Nobuya, Tsuchiya Yoshiki, Ohashi Munehiro, Minami Yoichi, Cui Guangwei, Asahi Takuma, Ono Ryutaro, Sasawaki Yuh, Konishi Eiichi, Yoo Seung-Hee, Chen Zheng, Teramukai Satoshi, Ikuta Koichi, Yagita Kazuhiro
  • Journal Title: Scientific Reports Volume: 10 Issue: 1 Pages: 2569-2569
  • DOI: 10.1038/s41598-020-59541-y
  • NAID: 120006799241
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Control of immunity by glucocorticoids (2019)
  • Author(s): Shimba Akihiro
  • Organizer: 第４８回日本免疫学会学術集会
  • Invited
• [Presentation] Glucocorticoids enhance T cell immune response. (2019)
  • Author(s): 榛葉旭恒
  • Organizer: 日本免疫学会
  • Invited