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

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

  • Cell Rep. 2019 Dec 24;29(13):4447-4459.e6. doi: 10.1016/j.celrep.2019.11.089.
Liisa Andersen 1,  Alexandra Franziska Gülich 1,  Marlis Alteneder 1,  Teresa Preglej 1,  Maria Jonah Orola 1,  Narendra Dhele 1,  Valentina Stolz 1,  Alexandra Schebesta 1,  Patricia Hamminger 1,  Anastasiya Hladik 2,  Stefan Floess 3,  Thomas Krausgruber 4,  Thomas Faux 5,  Syed Bilal Ahmad Andrabi 6,  Jochen Huehn 3,  Sylvia Knapp 7,  Tim Sparwasser 8,  Christoph Bock 9,  Asta Laiho 5,  Laura L Elo 5,  Omid Rasool 6,  Riitta Lahesmaa 6,  Shinya Sakaguchi 1,  Wilfried Ellmeier 10
Affiliations

Affiliations

  • 1 Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.
  • 2 Laboratory of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
  • 3 Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany.
  • 4 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 5 Medical Bioinformatics Centre, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
  • 6 Molecular Systems Immunology, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland.
  • 7 Laboratory of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria; CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
  • 8 Department of Medical Microbiology and Hygiene, Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • 9 CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria.
  • 10 Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria. Electronic address: wilfried.ellmeier@meduniwien.ac.at.
PMID: 31875552 DOI: 10.1016/j.celrep.2019.11.089
Abstract

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.

Keywords

DSS-induced colitis; FOXP3; MAZR; PATZ1; T(reg); regulatory T cells.

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