TCF1 and LEF1 Control Treg Competitive Survival and Tfr Development to Prevent Autoimmune Diseases
| Autor: | Bi-Huei Yang, Kristen Jepsen, Ke Wang, Xiaomei Yuan, Li-Fan Lu, Yan Liang, Shuo Wan, Wanqing Xu, Wenxian Fu, Sunglim Cho, Gen-Sheng Feng, Yi Dong, Hai-Hui Xue |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Helper-Inducer T-Lymphocytes Medical Physiology Autoimmunity Inbred C57BL medicine.disease_cause T-Lymphocytes Regulatory Mice 0302 clinical medicine Tfr homeostasis 2.1 Biological and endogenous factors Hepatocyte Nuclear Factor 1-alpha lcsh:QH301-705.5 Mice Knockout Competitive fitness autoimmunity FOXP3 Cell Differentiation hemic and immune systems T-Lymphocytes Helper-Inducer Regulatory competitive fitness 3. Good health regulatory T cells medicine.anatomical_structure Knockout mouse embryonic structures Female Lymphoid Enhancer-Binding Factor 1 Knockout chemical and pharmacologic phenomena Systemic autoimmunity Biology Autoimmune Disease Article General Biochemistry Genetics and Molecular Biology Autoimmune Diseases 03 medical and health sciences Genetics medicine Animals LEF1 TCF1 B cell Prevention Inflammatory and immune system Germinal center Germinal Center Mice Inbred C57BL 030104 developmental biology lcsh:Biology (General) Immunology Biochemistry and Cell Biology 030217 neurology & neurosurgery Homeostasis |
| Zdroj: | Cell Reports, Vol 27, Iss 12, Pp 3629-3645.e6 (2019) Cell reports, vol 27, iss 12 Cell reports |
| ISSN: | 2211-1247 |
| Popis: | SUMMARY CD4+ Foxp3+ T regulatory (Treg) cells are key players in preventing lethal autoimmunity. Tregs undertake differentiation processes and acquire diverse functional properties. However, how Treg’s differentiation and functional specification are regulated remains incompletely understood. Here, we report that gradient expression of TCF1 and LEF1 distinguishes Tregs into three distinct subpopulations, particularly highlighting a subset of activated Treg (aTreg) cells. Treg-specific ablation of TCF1 and LEF1 renders the mice susceptible to systemic autoimmunity. TCF1 and LEF1 are dispensable for Treg’s suppressive capacity but essential for maintaining a normal aTreg pool and promoting Treg’s competitive survival. As a consequence, the development of T follicular regulatory (Tfr) cells, which are a subset of aTreg, is abolished in TCF1/LEF1-conditional knockout mice, leading to unrestrained T follicular helper (Tfh) and germinal center B cell responses. Thus, TCF1 and LEF1 act redundantly to control the maintenance and functional specification of Treg subsets to prevent autoimmunity. Graphical Abstract In Brief Transcriptional regulation of Treg differentiation and function remains incompletely understood. Yang et al. report that two TCF family transcription factors regulate the survival and functional specification of a subset of Treg cells to prevent autoimmunity. |
| Databáze: | OpenAIRE |
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