The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3+ Regulatory T Cells
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
Affiliations
Liisa Andersen
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Alexandra Franziska Gülich
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Marlis Alteneder
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Teresa Preglej
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Maria Jonah Orola
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Narendra Dhele
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Valentina Stolz
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Alexandra Schebesta
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Patricia Hamminger
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Anastasiya Hladik
Laboratory of Infection Biology, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Stefan Floess
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Thomas Krausgruber
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
Thomas Faux
Medical Bioinformatics Centre, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Syed Bilal Ahmad Andrabi
Molecular Systems Immunology, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Jochen Huehn
Experimental Immunology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Sylvia Knapp
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
Tim Sparwasser
Department of Medical Microbiology and Hygiene, Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany
Christoph Bock
CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria; Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
Asta Laiho
Medical Bioinformatics Centre, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Laura L. Elo
Medical Bioinformatics Centre, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Omid Rasool
Molecular Systems Immunology, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Riitta Lahesmaa
Molecular Systems Immunology, Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku, Finland
Shinya Sakaguchi
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria
Wilfried Ellmeier
Division of Immunobiology, Institute of Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria; Corresponding author
Summary: 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. : 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. Keywords: MAZR, PATZ1, FOXP3, regulatory T cells, Treg, DSS-induced colitis
