T-regulatory cells require Sin3a for stable expression of Foxp3.

Lanette M Christensen, Tatiana Akimova, Liqing Wang, Rongxiang Han, Arabinda Samanta, Eros Di Giorgio, Wayne W Hancock

Frontiers in immunology 2024

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Histone deacetylases 1 and 2 play a major role in the transcriptional regulation of T-regulatory (Treg) cells via interactions with a myriad of coregulatory factors. Sin3a has been well established as a Hdac1/2 cofactor, while its role within Tregs has not been established. In this study, the effects of conditional deletion of Sin3a within Foxp3+ Tregs were evaluated. Developmental deletion of Sin3a from Foxp3+ Tregs resulted in the rapid onset of fatal autoimmunity. Treg numbers were greatly reduced, while residual Tregs had impaired suppressive function. Mice also showed effector T-cell activation, autoantibody production, and widespread tissue injury. Mechanistically, Sin3a deletion resulted in decreased transcription of Foxp3 with a complete lack of CNS2 CpG demethylation. In addition, Foxp3 protein stability was impaired with an increased ex-Treg population. Thus, Sin3a plays a critical role in the maintenance of Treg identity and function and is essential for the expression and stability of Foxp3. Copyright © 2024 Christensen, Akimova, Wang, Han, Samanta, Di Giorgio and Hancock.

Citation

Lanette M Christensen, Tatiana Akimova, Liqing Wang, Rongxiang Han, Arabinda Samanta, Eros Di Giorgio, Wayne W Hancock. T-regulatory cells require Sin3a for stable expression of Foxp3. Frontiers in immunology. 2024;15:1444937