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JunB Controls Intestinal Effector Programs in Regulatory T Cells.
Frontiers in Immunology ( IF 5.7 ) Pub Date : 2020-03-31 , DOI: 10.3389/fimmu.2020.00444
Joshua D Wheaton 1 , Maria Ciofani 1, 2
Affiliation  

Foxp3-expressing regulatory T (Treg) cells are critical mediators of immunological tolerance to both self and microbial antigens. Tregs activate context-dependent transcriptional programs to adapt effector function to specific tissues; however, the factors controlling tissue-specific gene expression in Tregs remain unclear. Here, we find that the AP-1 transcription factor JunB regulates the intestinal adaptation of Tregs by controlling select gene expression programs in multiple Treg subsets. Treg-specific ablation of JunB results in immune dysregulation characterized by enhanced colonic T helper cell accumulation and cytokine production. However, in contrast to its classical binding-partner BATF, JunB is dispensable for maintenance of effector Tregs as well as most specialized Treg subsets. In the Peyer's patches, JunB activates a transcriptional program facilitating the maintenance of CD25- Tregs, leading to the complete loss of T follicular regulatory cells in the absence of JunB. This defect is compounded by loss of a separate effector program found in both major colonic Treg subsets that includes the cytolytic effector molecule granzyme B. Therefore, JunB is an essential regulator of intestinal Treg effector function through pleiotropic effects on gene expression.

中文翻译:


JunB 控制调节性 T 细胞中的肠道效应器程序。



表达 Foxp3 的调节性 T (Treg) 细胞是对自身抗原和微生物抗原免疫耐受的关键介质。 Tregs 激活上下文相关的转录程序,使效应器功能适应特定组织;然而,控制Tregs中组织特异性基因表达的因素仍不清楚。在这里,我们发现 AP-1 转录因子 JunB 通过控制多个 Treg 亚群中的选择基因表达程序来调节 Treg 的肠道适应。 JunB 的 Treg 特异性消除会导致免疫失调,其特征是结肠 T 辅助细胞积累和细胞因子产生增强。然而,与其经典的结合伙伴 BATF 相比,JunB 对于效应 Treg 以及大多数特化 Treg 子集的维护是可有可无的。在派尔氏淋巴集结中,JunB 激活转录程序,促进 CD25-Treg 的维持,导致在没有 JunB 的情况下滤泡调节性 T 细胞完全丧失。这种缺陷因在两个主要结肠 Treg 亚群中发现的单独效应程序的缺失而变得更加复杂,其中包括溶细胞效应分子颗粒酶 B。因此,JunB 通过对基因表达的多效性作用而成为肠道 Treg 效应功能的重要调节剂。
更新日期:2020-04-01
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