Regulation of autoimmunity by the modulation of gut immunity.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H04218
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Juntendo University
• Principal Investigator: Miyake Sachiko 順天堂大学, 医学部, 教授 (50266045)
• Co-Investigator(Kenkyū-buntansha): 千葉 麻子 順天堂大学, 医学部, 准教授 (40532726)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 腸管免疫 / 腸内細菌 / 自己免疫 / 自然T細胞

Outline of Final Research Achievements

Accumulating evidence has indicated that gut environment is important for the development of autoimmune diseases (ADs). We found that the existence of dysbiosis in patients with multiple sclerosis characterized with the decrease of short-chain fatty acids and their producing bacteria. Among them, administration of Eubacterium rectale and Megamonas funiformis ameliorated experimental autoimmune encephalomyelitis. M. funiformis also reduced the demyelination in cuprizone-induced demyelination model. We revealed that mucosal-associated invariant T (MAIT) cells, mainly located in intestine, are involved in the exacerbation of disease of lupus model and colitis model using MR1 deficient mice. Moreover, we synthesized the inhibitory ligand for MAIT cells and it’s administration ameliorated the disease severity of these models. Further studies to reveal the mechanisms how MAIT cells aggravate these diseases will provide new therapeutic targets for the treatment and prevent of ADs.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

自己免疫性疾患の発症や増悪に腸内環境の重要性が明らかになり、関与する腸内細菌や免疫細胞が同定されたことは意義深い。これらの研究を発展させ、同定された腸内細菌や免疫細胞がどのように病態形成に関わるかを分子レベルで明らかにし、その制御法を開発することにより、自己免疫疾患の病態改善につながるばかりでなく、発症予防に応用できる可能性があり社会的意義が大きい。