Treg identity protection by an epigenetic switch
| Autor: | Xudong Li, Ye Zheng |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Ecology
Cellular differentiation Cell hemic and immune systems chemical and pharmacologic phenomena Forkhead Transcription Factors Cell Biology Cell fate determination Biology T-Lymphocytes Regulatory Article Cell biology Multicellular organism medicine.anatomical_structure medicine Animals Epigenetics Molecular Biology Reprogramming Homeostasis Function (biology) Developmental Biology |
| Zdroj: | Cell Cycle. 13:3159-3160 |
| ISSN: | 1551-4005 1538-4101 |
| Popis: | The homeostasis of multicellular organisms requires terminally differentiated cells to preserve their lineage specificity. However, it is unclear if mechanisms exist to actively protect cell identity in response to environmental cues that confer functional plasticity. Regulatory T (Treg) cells, specified by the transcription factor Foxp3, are indispensable for immune system homeostasis. Here, we report that conserved non-coding sequence 2 (CNS2), a CpG-rich Foxp3 intronic cis-element specifically demethylated in mature Tregs, helps maintain immune homeostasis and limit autoimmune disease development by protecting Treg identity in response to signals that shape mature Treg functions and drive their initial differentiation. In activated Tregs, CNS2 helps protect Foxp3 expression from destabilizing cytokine conditions by sensing TCR/NFAT activation, which facilitates the interaction between CNS2 and Foxp3 promoter. Thus, epigenetically marked cis-elements can protect cell identity by sensing key environmental cues central to both cell identity formation and functional plasticity without interfering with initial cell differentiation. |
| Databáze: | OpenAIRE |
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