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RESEARCH PRODUCT

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

Omid RasoolThomas FauxAnastasiya HladikTeresa PreglejSyed Bilal Ahmad AndrabiThomas KrausgruberAsta LaihoPatricia HammingerAlexandra Franziska GülichWilfried EllmeierNarendra DheleLiisa AndersenAlexandra SchebestaSylvia KnappSylvia KnappStefan FloessMaria Jonah OrolaChristoph BockChristoph BockLaura L. EloJochen HuehnValentina StolzShinya SakaguchiRiitta LahesmaaMarlis AltenederTim Sparwasser

subject

0301 basic medicineFOXP3PATZ1chemical and pharmacologic phenomenaBiologyTreg cellGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciences0302 clinical medicineIntestinal inflammationmedicineForkhead Box Protein P3Immune homeostasisColitisTranscription factorlcsh:QH301-705.5DSS-induced colitisMAZRT(reg)FOXP3hemic and immune systemsmedicine.diseaseCell biology030104 developmental biologyregulatory T cellslcsh:Biology (General)030217 neurology & neurosurgery

description

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

yearjournalcountryeditionlanguage
2019-12-24Cell Reports
10.1016/j.celrep.2019.11.089http://www.sciencedirect.com/science/article/pii/S2211124719315876