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 Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic T-reg cell development and during in-vitro-induced human Treg 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.