Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3

Kentaro Tanaka, Gustavo J. Martinez, Xiaowei Yan, Weiwen Long, Kenji Ichiyama, Xinxin Chi, Byung Seok Kim, Joseph M. Reynolds, Yeonseok Chung, Shinya Tanaka, Lan Liao, Yoichi Nakanishi, Akihiko Yoshimura, Pan Zheng, Xiaohu Wang, Qiang Tian, Jianming Xu, Bert W. O'Malley, Chen Dong

研究成果: ジャーナルへの寄稿記事

2 引用 (Scopus)

抄録

T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling.

元の言語英語
ページ(範囲)2318-2329
ページ数12
ジャーナルCell Reports
23
発行部数8
DOI
出版物ステータス出版済み - 5 22 2018

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Nuclear Receptor Coactivator 3
Th17 Cells
Cell Differentiation
Interleukin-1
Interleukin-6
Orphan Nuclear Receptors
Interleukin-23
T-cells
Interleukin-17
Microarray Analysis
Microarrays
Cytoplasmic and Nuclear Receptors
Helper-Inducer T-Lymphocytes
Gene expression
Transcriptional Activation
Autoimmune Diseases
Transcription Factors
Chemical activation
T-Lymphocytes
Gene Expression

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

これを引用

Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3. / Tanaka, Kentaro; Martinez, Gustavo J.; Yan, Xiaowei; Long, Weiwen; Ichiyama, Kenji; Chi, Xinxin; Kim, Byung Seok; Reynolds, Joseph M.; Chung, Yeonseok; Tanaka, Shinya; Liao, Lan; Nakanishi, Yoichi; Yoshimura, Akihiko; Zheng, Pan; Wang, Xiaohu; Tian, Qiang; Xu, Jianming; O'Malley, Bert W.; Dong, Chen.

:: Cell Reports, 巻 23, 番号 8, 22.05.2018, p. 2318-2329.

研究成果: ジャーナルへの寄稿記事

Tanaka, K, Martinez, GJ, Yan, X, Long, W, Ichiyama, K, Chi, X, Kim, BS, Reynolds, JM, Chung, Y, Tanaka, S, Liao, L, Nakanishi, Y, Yoshimura, A, Zheng, P, Wang, X, Tian, Q, Xu, J, O'Malley, BW & Dong, C 2018, 'Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3', Cell Reports, 巻. 23, 番号 8, pp. 2318-2329. https://doi.org/10.1016/j.celrep.2018.04.088
Tanaka, Kentaro ; Martinez, Gustavo J. ; Yan, Xiaowei ; Long, Weiwen ; Ichiyama, Kenji ; Chi, Xinxin ; Kim, Byung Seok ; Reynolds, Joseph M. ; Chung, Yeonseok ; Tanaka, Shinya ; Liao, Lan ; Nakanishi, Yoichi ; Yoshimura, Akihiko ; Zheng, Pan ; Wang, Xiaohu ; Tian, Qiang ; Xu, Jianming ; O'Malley, Bert W. ; Dong, Chen. / Regulation of Pathogenic T Helper 17 Cell Differentiation by Steroid Receptor Coactivator-3. :: Cell Reports. 2018 ; 巻 23, 番号 8. pp. 2318-2329.
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abstract = "T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling.",
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AU - Martinez, Gustavo J.

AU - Yan, Xiaowei

AU - Long, Weiwen

AU - Ichiyama, Kenji

AU - Chi, Xinxin

AU - Kim, Byung Seok

AU - Reynolds, Joseph M.

AU - Chung, Yeonseok

AU - Tanaka, Shinya

AU - Liao, Lan

AU - Nakanishi, Yoichi

AU - Yoshimura, Akihiko

AU - Zheng, Pan

AU - Wang, Xiaohu

AU - Tian, Qiang

AU - Xu, Jianming

AU - O'Malley, Bert W.

AU - Dong, Chen

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N2 - T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling.

AB - T helper 17 (Th17) cell development is programmed by the orphan nuclear receptor RORγt, but the underlying mechanism is not well understood. Nuclear receptor-mediated transcriptional activation depends on coactivators. Here, we show that steroid receptor coactivator-3 (SRC-3) critically regulates Th17 cell differentiation. Reduced incidence of experimental autoimmune encephalitis (EAE) associated with decreased Th17 cell generation in vivo was observed in mice with SRC-3 deletion specifically in T cells. In vitro, SRC-3 deficiency did not affect TGF-β/IL-6-induced Th17 cell generation but severely impaired pathogenic Th17 differentiation induced by IL-1/IL-6/IL-23. Microarray analysis revealed that SRC-3 not only regulates IL-17A but also IL-1R1 expression. SRC-3 bound to Il17a and Il1r1 loci in a RORγt-dependent manner and was required for recruitment of the p300 acetyltransferase. Thus, SRC-3 is critical for RORγt-dependent gene expression in Th17 cell-driven autoimmune diseases. The unique transcriptional programs in IL-1-induced inflammatory Th17 cells have remained unclear. Tanaka et al. demonstrate that SRC-3 in CD4+ T helper cells functions as a specific coactivator of RORγt, a master transcription factor of Th17 cells, by regulating IL-1-IL1R1 signaling.

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