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

Forkhead box protein P3+ (FOXP3+) regulatory T cells (Treg 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 Treg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic Treg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling Treg cell development. However, MAZR-deficient Treg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral Treg 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 Treg cell-intrinsic transcriptional network that modulates Treg cell development. Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

Citation

Liisa Andersen, Alexandra Franziska Gülich, Marlis Alteneder, Teresa Preglej, Maria Jonah Orola, Narendra Dhele, Valentina Stolz, Alexandra Schebesta, Patricia Hamminger, Anastasiya Hladik, Stefan Floess, Thomas Krausgruber, Thomas Faux, Syed Bilal Ahmad Andrabi, Jochen Huehn, Sylvia Knapp, Tim Sparwasser, Christoph Bock, Asta Laiho, Laura L Elo, Omid Rasool, Riitta Lahesmaa, Shinya Sakaguchi, Wilfried Ellmeier. The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3+ Regulatory T Cells. Cell reports. 2019 Dec 24;29(13):4447-4459.e6

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PMID: 31875552

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