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

被引:27
作者
Katagiri, Takaharu [1 ,2 ]
Yamazaki, Soh [1 ]
Fukui, Yuto [3 ]
Aoki, Kotaro [3 ]
Yagita, Hideo [4 ]
Nishina, Takashi [1 ]
Mikami, Tetuo [5 ]
Katagiri, Sayaka [6 ]
Shiraishi, Ayako [1 ]
Kimura, Soichiro [3 ]
Tateda, Kazuhiro [3 ]
Sumimoto, Hideki [7 ]
Endo, Shogo [8 ]
Kameda, Hideto [2 ]
Nakano, Hiroyasu [1 ,9 ]
机构
[1] Toho Univ, Dept Biochem, Sch Med, Ota Ku, 5-21-16 Omorinishi, Tokyo 1438540, Japan
[2] Toho Univ, Dept Internal Med, Div Rheumatol, Grad Sch Med,Ohashi Med Ctr,Meguro Ku, 2-22-36 Ohashi, Tokyo 1538515, Japan
[3] Toho Univ, Dept Microbiol & Infect Dis, Sch Med, Ota Ku, 5-21-16 Omorinishi, Tokyo 1438540, Japan
[4] Juntendo Univ, Dept Immunol, Grad Sch Med, Tokyo 1138421, Japan
[5] Toho Univ, Dept Pathol, Sch Med, Ota Ku, 5-21-16 Omorinishi, Tokyo 1438540, Japan
[6] Tokyo Med & Dent Univ, Grad Sch Med & Dent Sci, Dept Periodontol, Tokyo 1138510, Japan
[7] Kyushu Univ, Grad Sch Med Sci, Dept Biochem, Fukuoka, Fukuoka 8128582, Japan
[8] Tokyo Metropolitan Inst Gerontol, Aging Neurosci Res Team, Tokyo 1730015, Japan
[9] Toho Univ, Host Def Res Ctr, Sch Med, Ota Ku, 5-21-16 Omorinishi, Tokyo 1438540, Japan
基金
日本学术振兴会;
关键词
ROR-GAMMA-T; SODIUM-INDUCED COLITIS; MICE LACKING JUNB; ALPHA-CHAIN GENE; TARGET GENES; RECEPTOR; DIFFERENTIATION; INDUCTION; INNATE; MICROBIOTA;
D O I
10.1038/s41385-019-0182-0
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 (Junb(fl/fl)Cd4-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 Junb(fl/fl)Cd4-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 Junb(fl/fl)Cd4-Cre mice. Thus JunB plays a crucial role in the development of Treg cells by facilitating IL-2 signaling.
引用
收藏
页码:1104 / 1117
页数:14
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