Dual Mechanisms for Balancing Th17 and Treg Cell Fate by CREB
| Autor: | Wenjun Ouyang, Antony Symons |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Autoimmune diseases medicine.medical_treatment lcsh:Medicine Autoimmunity chemical and pharmacologic phenomena medicine.disease_cause CREB T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Immune system RAR-related orphan receptor gamma medicine Th17 cells Transcription factor lcsh:R5-920 biology lcsh:R FOXP3 Forkhead Transcription Factors hemic and immune systems General Medicine Regulatory T cells Nuclear Receptor Subfamily 1 Group F Member 3 030104 developmental biology Cytokine 030220 oncology & carcinogenesis Immunology biology.protein lcsh:Medicine (General) Treg cells Function (biology) Research Paper |
| Zdroj: | EBioMedicine, Vol 25, Iss C, Pp 20-21 (2017) EBioMedicine |
| ISSN: | 2352-3964 |
| Popis: | The molecular mechanisms that govern differential T cell development into pro-inflammatory Th17 vs. regulatory T (Treg) cells remain unclear. Here, we show that selective deletion of CREB in T cells or Th17 cells impaired Th17 cell differentiation in vitro and in vivo, and led to resistance to autoimmune diseases. Mechanistically, CREB, activated by CD3-PKC-ϴ signaling, plays a key role in regulating Th17 cell differentiation, at least in part through directly binding to the Il17-Il17f gene locus. Unexpectedly, although dispensable for FOXP3 expression and for the homeostasis and suppressive function of thymus-derived Treg cells, CREB negatively regulates the survival of TGF-β-induced Treg cells, and deletion of CREB resulted in increased FOXP3 + Treg cells in the intestine and protection in a colitis model. Thus, CREB is critical in autoimmune diseases by promoting Th17 cell and inhibiting de novo Treg cell generation. Highlights • CREB is critical for autoimmunity. • CREB plays a T cell- and Th17 cell-instrinsic role in controlling IL-17 expression and Th17 cell differentiation. • CREB is dispensable for FOXP3 expression and the homeostasis of nTreg cells. • CREB negatively regulates the survival of iTreg cells. The balance of Th17 and Treg cells dictates development of numerous autoimmune and inflammatory diseases, and targeting Th17 cell-related pathways has been proved to be effective in treatment of related diseases. Here, we identified CREB as a critical transcription factor in regulating the differentiation of Th17 cells and survival of Treg cells in both in vitro experimental systems and mouse models of autoimmune diseases. The findings in this study might be useful for developing therapeutics against Th17 cell-related immune diseases. |
| Databáze: | OpenAIRE |
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