| 研究実績の概要 |
Central tolerance functions cooperatively with peripheral tolerance, which limits the expansion and reactivity of autoreactive T cells in periphery. To eliminate the autoreactive T cells efficiently, mTECs ectopically express an enormous variety of proteins, which are expressed elsewhere in the body, named "tissue-restricted self-antigens (TRAs)”. The transcriptional regulators Aire and Fezf2 are mainly expressed by mTECs and are redundantly but independently involved in the induction of many TRAs. It is likely Aire induces transcriptionally inactive TRA genes through super enhancers, but Fezf2 directly regulates the TRAs expression through the transcriptional start sites. Eitheror Aire or Fezf2-deficient mice develop autoimmune phenotypes, indicating that they are required for the suppression of autoimmunity. However, the distinct features of Fezf2-dependent TRA genes expression from and Aire-dependent TRA genes are not well characterized and it is entirely unclear how TRA genes are induced by Fezf2 in mTECs. Here we explored the mechanism underlying the TRA expression regulated by Fezf2, and discovered a Fezf2-interacting molecule, which has the critical role for the Fezf2-dependent TRA expression in the epigenetic basis.
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