Transcription factor TFII-I fine tunes innate properties of B lymphocytes.

Transcription factor TFII-I fine tunes innate properties of B lymphocytes.
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转录因子TFII-I微调B淋巴细胞的先天特性。

DOI:
10.3389/fimmu.2023.1067459
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发表时间:
2023
影响因子:
7.3
通讯作者:
Roy, Ananda L.
Roy, Ananda L.
中科院分区:
医学2区
文献类型:
--
作者:
Singh, Amit;Kaileh, Mary;De, Supriyo;Mazan-Mamczarz, Krystyna;Bayarsaihan, Dashzeveg;Sen, Ranjan;Roy, Ananda L.

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广泛表达的转录因子TFII-I是一种多功能蛋白,在基因调控中具有多效性作用。TFII-I相关多态性与人类的干燥综合征和狼疮有关,小鼠Gtf 2 i基因的种系缺失导致胚胎致死。在这里,我们报告了一个独特的作用TFII-I的固有特性的B淋巴细胞的稳态。鼠B谱系细胞中Gtf 2 i的缺失导致转录组、染色质景观和相关转录因子结合位点的改变,其表现出骨髓样特征,并且与对LPS诱导的基因表达的增强的敏感性一致。TFII-I缺陷型B细胞也显示向IgG 3的转换增加,这是一种与炎症相关的表型。这些结果证明了TFII-I在维持免疫稳态中的作用,并为与人类B细胞主导的自身免疫性疾病相关的GTF 2 I多态性提供了线索。
The ubiquitously expressed transcription factor TFII-I is a multifunctional protein with pleiotropic roles in gene regulation. TFII-I associated polymorphisms are implicated in Sjögren’s syndrome and Lupus in humans and, germline deletion of the Gtf2i gene in mice leads to embryonic lethality. Here we report a unique role for TFII-I in homeostasis of innate properties of B lymphocytes. Loss of Gtf2i in murine B lineage cells leads to an alteration in transcriptome, chromatin landscape and associated transcription factor binding sites, which exhibits myeloid-like features and coincides with enhanced sensitivity to LPS induced gene expression. TFII-I deficient B cells also show increased switching to IgG3, a phenotype associated with inflammation. These results demonstrate a role for TFII-I in maintaining immune homeostasis and provide clues for GTF2I polymorphisms associated with B cell dominated autoimmune diseases in humans.
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