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

Forkhead box protein P3 + (FOXP3 + ) regulatory T cells (T reg 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 reg cells, while enforced MAZR expression impairs T reg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic T reg cell development and during in-vitro-induced human T reg cell differentiation, suggesting that MAZR protein levels are critical for controlling T reg cell development. However, MAZR-deficient T reg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral T reg 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 reg cell-intrinsic transcriptional network that modulates T reg cell development.