期刊
IMMUNOLOGY
卷 147, 期 4, 页码 367-376出版社
WILEY
DOI: 10.1111/imm.12575
关键词
mucosal homeostasis; mucosal immunity; T-bet; TBX21
类别
资金
- Wellcome Trust [091009, 107345]
- Medical Research Council [MR/M003493/1]
- National Institute for Health Research (NIHR) Biomedical Research Centre at Guy's and St Thomas and King's College London
- Biotechnology and Biological Sciences Research Council [BB/L010356/1] Funding Source: researchfish
- Crohn's & Colitis Foundation of America [504039] Funding Source: researchfish
- Medical Research Council [MR/N006445/1, MR/J006742/1, G0802068, MR/M003493/1] Funding Source: researchfish
- Rosetrees Trust [M596] Funding Source: researchfish
- BBSRC [BB/L010356/1] Funding Source: UKRI
- MRC [MR/M003493/1, MR/N006445/1, G0802068] Funding Source: UKRI
Initially understood to be a key regulator of interferon-gamma-producing helper T cells, our knowledge of T-bet's functional roles has expanded to encompass a growing range of cellular lineages. In addition to regulating other interferon-c-producing adaptive immune cells, it is now clear that T-bet plays a fundamental role in the regulation of innate immune responses across mucosal surfaces. This homeostatic role is demonstrated by the spontaneous colitis that occurs when T-bet is deleted from innate immune cells in RAG(-/-) mice. Using this model as a focal point, we review our understanding of T-bet's regulation of adaptive and innate immune systems, focusing particularly on mucosal populations including innate lymphoid cells, dendritic cells and intraepithelial lymphocytes. With the increasingly diverse effects of T-bet on different lineages, the classical binding-centric paradigm of T-bet's molecular functionality has increasingly struggled to account for the versatility of T-bet's biological effects. Recent recognition of the synergistic interactions between T-bet and other canonical transcription factors has led to a co-operative paradigm that has provided greater explanatory power. Synthesizing insights from ChIP-seq and comparative biology, we expand the co-operative paradigm further and suggest a network approach as a powerful way to understand and model T-bet's diverse functionality.
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