Abstract
T cell differentiation from naïve T cells to specialized effector subsets of mature cells is determined by the iterative action of transcription factors. At each stage of specific T cell lineage differentiation, transcription factor interacts not only with nuclear proteins such as histone and histone modifiers but also with other factors that are bound to the chromatin and play a critical role in gene expression. In this review, we focus on one of such nuclear protein known as tumor suppressor and scaffold matrix attachment region-binding protein 1 (SMAR1) in CD4+ T cell differentiation. SMAR1 facilitates Th1 differentiation by negatively regulating T-bet expression via recruiting HDAC1–SMRT complex to its gene promoter. In contrast, regulatory T (Treg) cell functions are dependent on inhibition of Th17-specific genes mainly IL-17 and STAT3 by SMAR1. Here, we discussed a critical role of chromatin remodeling protein SMAR1 in maintaining a fine-tuned balance between effector CD4+ T cells and Treg cells by influencing the transcription factors during allergic and autoimmune inflammatory diseases.
Highlights
Various subsets of T lymphocytes play a central role in vertebrate adaptive immune response
Various MAR-binding nuclear proteins are involved in crosstalk between genetic and epigenetic factors during differentiation of naïve T cells through chromatin changes
Studying “adaptor proteins” that bind to chromatin and define chromatin conformation provides us with cues to understand the mechanism of T cell differentiation
Summary
Various subsets of T lymphocytes play a central role in vertebrate adaptive immune response. Our lab provided the evidence that the expression of Th1-specific lineage commitment transcriptional factor T-bet could be regulated by SMAR1 and enhanced expression of SMAR1 caused defective Th1 response with a reciprocal increase in Th2 cell commitment [41] This inverse correlation of Th1/Th2 axis has been substantiated by many previous reports describing the differential function of proteins involved in the lineage specifications of T cell development [42, 43]. This observation is in line with the previous reports suggesting the elevated T-bet expression in SMAR1−/− mice after chronic allergic antigen exposure [41, 71, 73] It shows SMAR1 is a novel and essential factor for the establishment of Th2 cells by functioning as a Th1-specific transcriptional gene repressor. Though the studies so far have elucidated the role of SMAR1 with respect to tumor suppressor, our recent studies initiated to establish the anti-inflammatory function of SMAR1 in autoimmune disorders like EAE and IBD
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