Control of regulatory T‐cell differentiation and function by T‐cell receptor signalling and Foxp3 transcription factor complexes
| Autor: | Masahiro Ono |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
LUNG-DISEASE
0301 basic medicine Transcription Genetic TCR signalling ROR-GAMMA-T NF-KAPPA-B Transcription factor complex NUCLEAR-FACTOR Lymphocyte Activation T-Lymphocytes Regulatory NF-κB Epigenesis Genetic protein-protein interaction Mice 0302 clinical medicine Runx1 RAR-related orphan receptor gamma Transcriptional regulation Immunology and Allergy transcriptional regulation Review Articles transcription factor ENHANCER LANDSCAPE GENE-EXPRESSION AML1/Runx1 Regulation of gene expression Cell Differentiation Forkhead Transcription Factors NFAT hemic and immune systems Cell biology 1107 Immunology Foxp3 Corrigendum Life Sciences & Biomedicine Signal Transduction Regulatory T cell differentiation Immunology Receptors Antigen T-Cell p300 chemical and pharmacologic phenomena Biology Models Biological Enhanceosome 03 medical and health sciences Animals Humans Cell Lineage IMMUNE TOLERANCE Transcription factor CLONAL EXPANSION DEPENDENT KINASE Science & Technology AML1 regulatory T-cells 030104 developmental biology Th17 Cells LYMPHORETICULAR DISEASE 1114 Paediatrics and Reproductive Medicine Protein Processing Post-Translational 030215 immunology |
| Zdroj: | Immunology |
| Popis: | The transcription factor Foxp3 controls the differentiation and function of regulatory T-cells (Treg). Studies in the past decades identified numerous Foxp3-interacting protein partners. However, it is still not clear how Foxp3 produces the Treg-type transcriptomic landscape through cooperating with its partners. Here I show the current understanding of how Foxp3 transcription factor complexes regulate the differentiation, maintenance, and functional maturation of Treg. Importantly, T-cell receptor (TCR) signalling plays central roles in Treg differentiation and Foxp3-mediated gene regulation. Thus, differentiating Treg will have recognised their cognate antigens and received TCR signals before initiating Foxp3 transcription, which is triggered by TCR induced transcription factors including NFAT, AP-1, and NF-κB. Once expressed, Foxp3 seizes TCR signal-induced transcriptional and epigenetic mechanisms through interacting with is AML1/Runx1 and NFAT. Thus Foxp3 modifies gene expression dynamics of TCR-induced genes, which constitute cardinal mechanisms for Treg-mediated immune suppression. Next, I discuss the following key topics, proposing new mechanistic models for Foxp3-mediated gene regulation: (1) how Foxp3 transcription is induced and maintained by the Foxp3-inducing enhanceosome and the Foxp3 autoregulatory transcription factor complex; (2) molecular mechanisms for effector Treg differentiation (i.e. Treg maturation); (3) how Foxp3 activates or represses its target genes through recruiting coactivators and corepressors; (4) the 'decision-making' Foxp3-containing transcription factor complex for Th17 and Treg differentiation; and (5) the roles of post-translational modification in Foxp3 regulation. Thus, this article provides cutting-edge understanding of molecular biology of Foxp3 and Treg, integrating findings by biochemical and genomic studies. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|