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Differential regulation of transcription factor T-bet induction during NK cell development and T helper-1 cell differentiation
Immunity ( IF 32.4 ) Pub Date : 2022-04-04 , DOI: 10.1016/j.immuni.2022.03.005
Difeng Fang 1 , Kairong Cui 2 , Yaqiang Cao 2 , Mingzhu Zheng 3 , Takeshi Kawabe 4 , Gangqing Hu 5 , Jaspal S Khillan 6 , Dan Li 7 , Chao Zhong 8 , Dragana Jankovic 9 , Alan Sher 10 , Keji Zhao 2 , Jinfang Zhu 1
Affiliation  

Adaptive CD4+ T helper cells and their innate counterparts, innate lymphoid cells, utilize an identical set of transcription factors (TFs) for their differentiation and functions. However, similarities and differences in the induction of these TFs in related lymphocytes are still elusive. Here, we show that T helper-1 (Th1) cells and natural killer (NK) cells displayed distinct epigenomes at the Tbx21 locus, which encodes T-bet, a critical TF for regulating type 1 immune responses. The initial induction of T-bet in NK precursors was dependent on the NK-specific DNase I hypersensitive site Tbx21-CNS-3, and the expression of the interleukin-18 (IL-18) receptor; IL-18 induced T-bet expression through the transcription factor RUNX3, which bound to Tbx21-CNS-3. By contrast, signal transducer and activator of transcription (STAT)-binding motifs within Tbx21-CNS-12 were critical for IL-12-induced T-bet expression during Th1 cell differentiation both in vitro and in vivo. Thus, type 1 innate and adaptive lymphocytes utilize distinct enhancer elements for their development and differentiation.



中文翻译:

NK细胞发育和T helper-1细胞分化过程中转录因子T-bet诱导的差异调节

适应性 CD4 + T 辅助细胞及其先天对应物、先天淋巴样细胞利用一组相同的转录因子 (TF) 来实现其分化和功能。然而,这些 TF 在相关淋巴细胞中的诱导异同仍然难以捉摸。在这里,我们表明 T 辅助细胞 1 (Th1) 细胞和自然杀伤 (NK) 细胞在Tbx21位点显示出不同的表观基因组,该位点编码 T-bet,一种调节 1 型免疫反应的关键 TF。NK 前体中 T-bet 的初始诱导依赖于 NK 特异性 DNase I 超敏位点Tbx21-CNS-3和白细胞介素 18 (IL-18) 受体的表达;IL-18 通过转录因子 RUNX3 诱导 T-bet 表达,该转录因子与Tbx21-CNS-3。相比之下,Tbx21-CNS-12内的信号转导和转录激活因子 (STAT) 结合基序对于 Th1 细胞体外体内分化期间 IL-12 诱导的 T-bet 表达至关重要。因此,1 型先天性和适应性淋巴细胞利用不同的增强子元件进行发育和分化。

更新日期:2022-04-04
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