JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling.,Mucosal Immunology

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JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling.
Mucosal Immunology ( IF 7.9 ) Pub Date : 2019-07-08 , DOI: 10.1038/s41385-019-0182-0
Takaharu Katagiri _{1,

2} , Soh Yamazaki ₁ , Yuto Fukui ₃ , Kotaro Aoki ₃ , Hideo Yagita ₄ , Takashi Nishina ₁ , Tetuo Mikami ₅ , Sayaka Katagiri ₆ , Ayako Shiraishi ₁ , Soichiro Kimura ₃ , Kazuhiro Tateda ₃ , Hideki Sumimoto ₇ , Shogo Endo ₈ , Hideto Kameda ₂ , Hiroyasu Nakano _{1,

9}

Affiliation

Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
Division of Rheumatology, Department of Internal Medicine, Toho University Graduate School of Medicine (Ohashi Medical Center), 2-22-36 Ohashi, Meguro-ku, Tokyo, 153-8515, Japan.
Department of Microbiology and Infectious Diseases, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
Department of Immunology, Juntendo University Graduate School of Medicine, Tokyo, 113-8421, Japan.
Department of Pathology, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.
Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8510, Japan.
Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, Fukuoka, 812-8582, Japan.
Aging Neuroscience Research Team, Tokyo Metropolitan Institute of Gerontology, Tokyo, 173-0015, Japan.
Host Defense Research Center, Toho University School of Medicine, 5-21-16 Omorinishi, Ota-ku, Tokyo, 143-8540, Japan.

The AP-1 transcription factor JunB plays crucial roles in multiple biological processes, including placental formation and bone homeostasis. We recently reported that JunB is essential for development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4+ T cells (Junbfl/flCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis because of impaired development of regulatory T (Treg) cells. Production of interleukin (IL)-2 and expression of CD25, a high affinity IL-2 receptor component, were decreased in Junb-deficient CD4+ T cells in vitro and in vivo. Naive CD4+ T cells from Junbfl/flCd4-Cre mice failed to differentiate into Treg cells in the absence of exogenously added IL-2 in vitro. A mixed bone marrow transfer experiment revealed that defective Treg development of Junb-deficient CD4+ T cells was not rescued by co-transferred wild-type cells, indicating a significance of the cell-intrinsic defect. Injection of IL-2-anti-IL-2 antibody complexes induced expansion of Treg cells and alleviated DSS-induced colitis in Junbfl/flCd4-Cre mice. Thus JunB plays a crucial role in the development of Treg cells by facilitating IL-2 signaling.

中文翻译：

JunB 通过促进 IL-2 信号传导在调节性 T 细胞的发育中起着至关重要的作用。

AP-1 转录因子 JunB 在多种生物过程中起着至关重要的作用，包括胎盘形成和骨稳态。我们最近报道 JunB 对 Th17 细胞的发育至关重要，因此 Junb 缺陷小鼠对实验性自身免疫性脑脊髓炎有抵抗力。然而，JunB 在其他炎症性疾病条件下对 CD4+ T 细胞的作用尚不清楚。在这里，我们显示 CD4+ T 细胞中缺乏 JunB 的小鼠（Junbfl/flCd4-Cre 小鼠）由于调节性 T (Treg) 细胞的发育受损而更易患葡聚糖硫酸钠 (DSS) 诱导的结肠炎。在体外和体内 Junb 缺陷型 CD4+ T 细胞中，白细胞介素 (IL)-2 的产生和高亲和力 IL-2 受体成分 CD25 的表达均降低。在没有外源添加的 IL-2 的情况下，来自 Junbfl/flCd4-Cre 小鼠的幼稚 CD4+ T 细胞无法在体外分化为 Treg 细胞。混合骨髓移植实验表明，Junb 缺陷型 CD4+ T 细胞的 Treg 发育缺陷未被共转移的野生型细胞挽救，表明细胞固有缺陷的重要性。在 Junbfl/flCd4-Cre 小鼠中，注射 IL-2-抗 IL-2 抗体复合物可诱导 Treg 细胞扩增并减轻 DSS 诱导的结肠炎。因此，JunB 通过促进 IL-2 信号传导在 Treg 细胞的发育中起着至关重要的作用。表明细胞内在缺陷的重要性。在 Junbfl/flCd4-Cre 小鼠中，注射 IL-2-抗 IL-2 抗体复合物可诱导 Treg 细胞扩增并减轻 DSS 诱导的结肠炎。因此，JunB 通过促进 IL-2 信号传导在 Treg 细胞的发育中起着至关重要的作用。表明细胞内在缺陷的重要性。在 Junbfl/flCd4-Cre 小鼠中，注射 IL-2-抗 IL-2 抗体复合物可诱导 Treg 细胞扩增并减轻 DSS 诱导的结肠炎。因此，JunB 通过促进 IL-2 信号传导在 Treg 细胞的发育中起着至关重要的作用。

更新日期：2019-11-18

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