The Transcription Factor MAZR/PATZ1 Regulates the Development of FOXP3+ Regulatory T Cells
| Autor: | Omid Rasool, Thomas Faux, Anastasiya Hladik, Teresa Preglej, Syed Bilal Ahmad Andrabi, Thomas Krausgruber, Asta Laiho, Patricia Hamminger, Alexandra Franziska Gülich, Wilfried Ellmeier, Narendra Dhele, Liisa Andersen, Alexandra Schebesta, Sylvia Knapp, Stefan Floess, Maria Jonah Orola, Christoph Bock, Laura L. Elo, Jochen Huehn, Valentina Stolz, Shinya Sakaguchi, Riitta Lahesmaa, Marlis Alteneder, Tim Sparwasser |
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| Přispěvatelé: | HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
FOXP3 PATZ1 chemical and pharmacologic phenomena Biology Treg cell General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Intestinal inflammation medicine Forkhead Box Protein P3 Immune homeostasis Colitis Transcription factor lcsh:QH301-705.5 DSS-induced colitis MAZR T(reg) hemic and immune systems medicine.disease Cell biology 030104 developmental biology regulatory T cells lcsh:Biology (General) 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 29, Iss 13, Pp 4447-4459.e6 (2019) Cell reports |
| ISSN: | 2211-1247 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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