JunB is essential for IL-23-dependent pathogenicity of Th17 cells.
JunB is essential for IL-23-dependent pathogenicity of Th17 cells.
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DOI：
10.1038/ncomms15628
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发表时间：
2017-05-30
影响因子：
16.6
通讯作者：
Ishikawa H
中科院分区：
文献类型：
--
作者：
Hasan Z;Koizumi SI;Sasaki D;Yamada H;Arakaki N;Fujihara Y;Okitsu S;Shirahata H;Ishikawa H
产生白细胞介素-17（IL-17）的CD 4 + T辅助细胞，称为T辅助17（TH 17）细胞，包括表现出不同致病性的异质亚群。虽然致病性和非致病性TH 17亚群共享共同的RORγ t依赖性TH 17转录程序，但这些亚群中的每一个的特异性转录调控机制大多是未知的。在这里，我们表明AP-1转录因子JunB是TH 17致病性的关键。在IL-23依赖的致病性TH 17细胞中，由IL-6诱导的JunB通过促进BATF在Rorc位点的DNA结合而对RORγt和IL-23受体的表达至关重要，但在TGF-β1依赖的非致病性TH 17细胞中则不然。Junb缺陷型T细胞不能诱导TH 17介导的自身免疫性脑脊髓炎和结肠炎。然而，JunB缺乏并不影响肠道驻留的非致病性TH 17细胞的丰度。JunB对IL-23依赖性TH 17致病性的选择性需求表明JunB依赖性途径可能是自身免疫性疾病的治疗靶点。辅助性T细胞17（Th 17）可能是致病性的，但控制这种表型的是什么尚不清楚。在这里，作者表明转录因子JunB通过调节多个Th 17相关基因的转录来促进促炎性Th 17功能。
CD4+ T-helper cells producing interleukin-17 (IL-17), known as T-helper 17 (TH17) cells, comprise heterogeneous subsets that exhibit distinct pathogenicity. Although pathogenic and non-pathogenic TH17 subsets share a common RORγt-dependent TH17 transcriptional programme, transcriptional regulatory mechanisms specific to each of these subsets are mostly unknown. Here we show that the AP-1 transcription factor JunB is critical for TH17 pathogenicity. JunB, which is induced by IL-6, is essential for expression of RORγt and IL-23 receptor by facilitating DNA binding of BATF at the Rorc locus in IL-23-dependent pathogenic TH17 cells, but not in TGF-β1-dependent non-pathogenic TH17 cells. Junb-deficient T cells fail to induce TH17-mediated autoimmune encephalomyelitis and colitis. However, JunB deficiency does not affect the abundance of gut-resident non-pathogenic TH17 cells. The selective requirement of JunB for IL-23-dependent TH17 pathogenicity suggests that the JunB-dependent pathway may be a therapeutic target for autoimmune diseases. T helper 17 (Th17) cells can be pathogenic, but what controls this phenotype is unclear. Here the authors show that the transcription factor JunB promotes proinflammatory Th17 function by regulating the transcription of multiple Th17-related genes.