期刊
CELL REPORTS
卷 29, 期 13, 页码 4447-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2019.11.089
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资金
- Biocenter Finland
- ELIXIR Finland
- Austrian Science Fund (FWF) [P23641, P26193, P29790, I00698]
- FWF special research program [SFB F70]
- FWF [P27747]
- Medical University of Vienna [DK W1212]
- German Research Foundation [SFB738]
- European Research Council ERC [677943]
- Academy of Finland [296801, 304995, 310561, 313343]
- Juvenile Diabetes Research Foundation JDRF [2-2013-32]
- Sigrid Juselius Foundation
- University of Turku
- Abo Akademi University
- Turku Graduate School (UTUGS)
- Academy of Finland (AoF) Centre of Excellence in Molecular Systems Immunology and Physiology Research (2012-2017) [250114]
- AoF [292335, 294337, 292482, 319280, 31444]
- Finnish Cancer Foundation
- European Union's Horizon 2020 Research and Innovation Program (ENLIGHT-TEN Innovative Training Network under the Marie Sklodowska-Curie grant) [675395]
- Austrian Science Fund (FWF) [P23641, P26193, P27747, P29790] Funding Source: Austrian Science Fund (FWF)
Forkhead box protein P3(+) (FOXP3(+)) regulatory T cells (T-reg 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 T-reg cells, while enforced MAZR expression impairs Treg cell differentiation. Further, MAZR expression levels are progressively downregulated during thymic T-reg cell development and during in-vitro-induced human Treg cell differentiation, suggesting that MAZR protein levels are critical for controlling T-reg cell development. However, MAZR-deficient T-reg cells show only minor transcriptional changes ex vivo, indicating that MAZR is not essential for establishing the transcriptional program of peripheral T-reg 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 T-reg cell-intrinsic transcriptional network that modulates T-reg cell development.
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