The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3 Regulatory T Cells.

Forkhead box protein P3 (FOXP3) regulatory T cells (T cells) play a key role in maintaining tolerance and immune homeostasis. Here, we report that a T cell-specific deletion of the transcription factor MAZR (also known as PATZ1) leads to an increased frequency of T cells, while enforced MAZR expression impairs T cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic T cell development and during in-vitro-induced human T cell differentiation, suggesting that MAZR protein levels are critical for controlling T cell development. However, MAZR-deficient T cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral T cells. Finally, the loss of MAZR reduces the clinical score in dextran-sodium sulfate (DSS)-induced colitis, suggesting that MAZR activity in T cells controls the extent of intestinal inflammation. Together, these data indicate that MAZR is part of a T cell-intrinsic transcriptional network that modulates T cell development.