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

• Published in: Cell reports (Cambridge) Vol. 29; no. 13; pp. 4447 - 4459.e6
• Main Authors: Andersen, Liisa, Gülich, Alexandra Franziska, Alteneder, Marlis, Preglej, Teresa, Orola, Maria Jonah, Dhele, Narendra, Stolz, Valentina, Schebesta, Alexandra, Hamminger, Patricia, Hladik, Anastasiya, Floess, Stefan, Krausgruber, Thomas, Faux, Thomas, Andrabi, Syed Bilal Ahmad, Huehn, Jochen, Knapp, Sylvia, Sparwasser, Tim, Bock, Christoph, Laiho, Asta, Elo, Laura L., Rasool, Omid, Lahesmaa, Riitta, Sakaguchi, Shinya, Ellmeier, Wilfried
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24-12-2019; Elsevier
• Subjects: Animals; Cell Differentiation; Colitis - immunology; Dextran Sulfate; DSS-induced colitis; Forkhead Transcription Factors - metabolism; FOXP3; Humans; Kruppel-Like Transcription Factors - metabolism; MAZR; Mice, Knockout; Neoplasm Proteins - metabolism; PATZ1; regulatory T cells; Repressor Proteins - metabolism; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - metabolism; Thymus Gland - cytology; Transcription, Genetic; Treg; DSS-induced colitis; regulatory T cells; PATZ1; FOXP3; Treg; MAZR; T(reg)
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2019.11.089

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.
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•FOXP3+ Treg cell generation is enhanced upon deletion of MAZR•Enforced expression of MAZR impairs Treg cell generation•MAZR expression levels are downregulated during Treg cell differentiation•T cell-specific deletion of MAZR reduces clinical score of DSS-induced colitis
FOXP3+ Treg cells are essential for maintaining tolerance and immune homeostasis. Andersen et al. reveal that MAZR is an important factor in regulating the delicate balance of Treg cell generation and report that MAZR expression levels play a key role in controlling Treg cell development and differentiation.