Identification of the transcriptinal regulator that controls functions of thymic epithelial cells required for immune tolerance
Description: Thymus generates self-tolerant T cells in the body, for which thymic epithelial cells in the medullary region (mTECs) play essential roles, thereby preventing the onset of autoimmune diseases. mTECs act as antigen presenting cells for several thousand promiscuously expressed tissue-specific antigens (TSAs), which are regulated by transcriptional regulator Aire and Fezf2. In this study, we sought to identify regulators of TSA expression in mTECs that operate independently of Aire and Fezf2. We describe that transcriptional regulator Ascl1 controls expressions of Aire- and Fezf2-independnt TSAs. Ascl1 is preferentially expressed in mTECs expressing lower level of CD80, which exhibit minimum Aire expression. Ascl1 deletion provokes autoimmunity in several organs. Mechanistically, expression of Ascl1 results in opening chromatin structure of TSA genes. Overall, our data suggests a novel Ascl1-dependent mechanism of TSA expression critical for suppressing onset of autoimmunity.
Amount: ¥17,420,000
Funding type: research
Funder scheme: Grant-in-Aid for Scientific Research (B)
Start date: 2017-04-01
End date: 2020-03-31
Investigator: Taishin Akiyama
Institution: Institute of Physical and Chemical Research
Funded outputs count: 14
Funder award ID: 17H04038
OpenAlex ID: G6913301475