The AP-1 transcription factor JunB is required for Th17 cell differentiation

Yamazaki, Soh; Tanaka, Yoshihiko; Araki, Hiromitsu; Kohda, Akira; Sanematsu, Fumiyuki; Arasaki, Tomoko; Duan, Xuefeng; Miura, Fumihito; Katagiri, Takamasa; Shindo, Ryodai; Nakano, Hiroyasu; Ito, Takashi; Fukui, Yoshihiro; Endo, Shogo; Sumimoto, Hideki

doi:10.1038/s41598-017-17597-3

Cited by 54 publications

(79 citation statements)

References 61 publications

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“…We further dissected the molecular mechanism by which IL4 and DTA-1 stimulation triggers the differentiation of na€ ve CD4 þ T cells into IL21-expressing CD4 þ T cells. To this end, we examined the mRNA expression of the transcription factors involved in transcription of IL21, including AP-1 transcription factors (35)(36)(37)(38). We found that Maf mRNA was increased by stimulation with IL4 and DTA-1 to a peak at 18 hours of stimulation ( Fig.…”

Section: Il4 Is Required For Dta-1-induced Il21-producing Tfh Cellsmentioning

confidence: 99%

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Koh

Kim

Shin

et al. 2020

Cancer Immunology Research

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Although treatment with the glucocorticoid-induced tumor necrosis factor receptor-related protein (GITR) agonistic antibody (DTA-1) has shown antitumor activity in various tumor models, the underlying mechanism is not fully understood. Here, we demonstrate that interleukin (IL)-21-producing follicular helper T (Tfh) cells play a crucial role in DTA-1-induced tumor inhibition. The administration of DTA-1 increased IL21 expression by Tfh cells in an antigen-specific manner, and this activation led to enhanced antitumor cytotoxic T lymphocyte (CTL) activity. Mice treated with an antibody that neutralizes the IL21 receptor exhibited decreased antitumor activity when treated with DTA-1. Tumor growth inhibition by DTA-1 was abrogated in Bcl6 fl/fl Cd4 Cre mice, which are genetically deficient in Tfh cells. IL4 was required for optimal induction of IL21-expressing Tfh cells by GITR costimulation, and c-Maf mediated this pathway. Thus, our findings identify GITR costimulation as an inducer of IL21-expressing Tfh cells and provide a mechanism for the antitumor activity of GITR agonism.

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Section: Il4 Is Required For Dta-1-induced Il21-producing Tfh Cellsmentioning

confidence: 99%

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Koh

Kim

Shin

et al. 2020

Cancer Immunology Research

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“…IL‐23 was demonstrated to directly regulate Blimp‐1 expression, synergizing with RORγt in the differentiation of Th17 cells during inflammation . BATF also played a key role in Th17 cell differentiation via binding the promoter regions of IL‐17A, IL‐17F, IL‐21, and IL‐22 . Nevertheless, cytokines, such as IL‐2 and IL‐27, were shown to inhibit Th17 cell differentiation .…”

Section: Phenotype and Differentiation Of Th17 Cellsmentioning

confidence: 99%

Th17 cell pathogenicity and plasticity in rheumatoid arthritis

Yang

Qian

Zhang

et al. 2019

Journal of Leukocyte Biology

117

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CD4 + Th cells play an important role in the development of rheumatoid arthritis (RA) by regulating adaptive immune response. As major subsets of CD4 + Th cells, Th17 cells can produce a large number of hallmark cytokines such as IL-17A and IL-17F, which participate in host defense and immune homeostasis. However, increasing researches have shown that Th17 cells are unstable and exhibit a certain degree of plasticity, which aggravates their pathogenicity. Furthermore, the plasticity and pathogenicity of Th17 cells are closely related with the disease activity in RA. In this paper, the characteristics including phenotype, differentiation, plasticity, and pathogenicity of Th17 cells in RA will be systematically summarized. This will contribute to clarify the immunologic mechanism of RA and further provide a novel strategy for the clinical treatment of autoimmune diseases. K E Y W O R D S pathogenicity, plasticity, rheumatoid arthritis, Th17 cells 1

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“…Recently we and other groups have reported that JunB is essential for the development of IL-17producing helper T (Th17) cells, and thus Junb-deficient mice are completely resistant to experimental autoimmune encephalomyelitis (EAE). [5][6][7] In addition, the transfer of CD45RB hi CD25 − CD4 + T cells from Junb-deficient mice to Rag1-deficient mice fails to induce colitis, 6 suggesting that JunB is indispensable for pathogenicity of T cells in these autoimmune diseases. On the other hand, it is unclear whether JunB in CD4 + T cells is involved in other inflammatory diseases such as those induced by innate immune cells.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2019

Self Cite

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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.

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The AP-1 transcription factor JunB is required for Th17 cell differentiation

Cited by 54 publications

References 61 publications

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

GITR Agonism Triggers Antitumor Immune Responses through IL21-Expressing Follicular Helper T Cells

Th17 cell pathogenicity and plasticity in rheumatoid arthritis

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

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