Effect of Fgf21 on autoimmunitiy and tumor immunity

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15454
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: Masuda Yuki 神戸薬科大学, 薬学部, 助教 (40421284)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: Fgf21 / 胸腺 / 実験的自己免疫性脳脊髄炎 / 樹状細胞

Outline of Final Research Achievements

In the thymus, medullary thymic epithelial cells (TECs) and dendritic cells (DCs) regulate central tolerance through elimination of autoreactive T cells. Disruption of self-tolerance induces autoimmune diseases. We have previously shown that Fibroblast growth factor 21 (Fgf21) is expressed in TECs and acts as intrathymic cytokine, inducing thymocyte development. However, the effect of Fgf21 on peripheral T cell response is still unknown.
This study shows that knockout of Fgf21 accelerated progression of experimental autoimmune encephalomyelitis, and Fgf21 knockout mice showed lower thymic DCs and higher T cell infiltration into central nervous system than wild-type mice. These results suggest that Fgf21 could inhibit autoimmune response, by directly or indirectly increased thymic DCs which facilitate elimination of autoreactive T cells, and shed light on its potential as a therapeutic target.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

自己免疫疾患の多くは難治性で、原因も明確でないことから難病に指定されており、その発症機序の解明や新たな治療法の開発が求められている。本研究では、臨床症状や免疫学的側面において多発性硬化症と多くの共通点を示す疾患モデルである実験的自己免疫性脳脊髄炎を用いてFgf21の影響について検討した。本研究でFgf21が自己免疫を抑制することが示唆されたため、Fgf21を用いた自己免疫疾患の新たな治療法の開発が期待できる。