The regulation of the ubiquitin-editing protein A20 in thymic selection

2018 Fiscal Year Annual Research Report

• Project/Area Number: 17K17916
• Research Institution: Hiroshima University
• Principal Investigator: 郭 芸 広島大学, 医歯薬保健学研究科(医), 助教 (50609766)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: A20 / thymic selection

Outline of Annual Research Achievements

According to the plan in H30, we continue analyzing the function of A20 in thymic selection. It is well known that the thymic selection is regulated by TCR signal. To assess the TCR signal pathway and related molecules in A20 cKO mice, we performed in vitro cell culture and western blotting etc. We found that the increase of Treg cells in A20 cKO mice was related with the changed TCR signal. The result of RNA-sequencing analysis also further confirmed the similar results. Moreover, by using HY TCR transgenic mice, we found that the deletion of A20 in T cell could not clearly affect the positive and negative selection.
Next, to further examine the function of A20 deficient Treg cells, we tried two mouse models. One is the tumor formation assay. We found that the size of tumor grew on A20 KO mice was significantly bigger than that of on the control mice, and more Treg cells appeared in the tumor. So, loss of A20 in T cell will impair antitumor immunity in mice. The other model is experimental autoimmune encephalomyelitis (EAE) induction. We found that T cell-specific A20 deletion could reduce the severity of the EAE induction in mice.
Now, we are trying to examine the role of thymic microenvironment in thymic selection by using A20 deficient mice in thymic epithelial cells. In addition, we are going to publish our data in a scientific journal.