TY - JOUR
T1 - Trim33 mediates the proinflammatory function of Th17 cells
AU - Tanaka, Shinya
AU - Jiang, Yu
AU - Martinez, Gustavo J.
AU - Tanaka, Kentaro
AU - Yan, Xiaowei
AU - Kurosaki, Tomohiro
AU - Kaartinen, Vesa
AU - Feng, Xin Hua
AU - Tian, Qiang
AU - Wang, Xiaohu
AU - Dong, Chen
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (31630022 and 91642201 to C. Dong) and Ministry of Science and Technology of China (2016YFC0906200 to C. Dong). C. Dong is a Bayer Chair Professor at Tsinghua University. The authors declare no competing financial interests.
Publisher Copyright:
© 2018 Tanaka et al.
PY - 2018/7/1
Y1 - 2018/7/1
N2 - Transforming growth factor–β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.
AB - Transforming growth factor–β (TGF-β) regulates reciprocal regulatory T cell (T reg) and T helper 17 (Th17) differentiation, the underlying mechanism of which is still not understood. Here, we report that tripartite motif-containing 33 (Trim33), a modulator of TGF-β signaling that associates with Smad2, regulates the proinflammatory function of Th17 cells. Trim33 deficiency in T cells ameliorated an autoimmune disease in vivo. Trim33 was required for induction in vitro of Th17, but not T reg cells. Moreover, Smad4 and Trim33 play contrasting roles in the regulation of IL-10 expression; loss of Trim33 enhanced IL-10 production. Furthermore, Trim33 was recruited to the Il17a and Il10 gene loci, dependent on Smad2, and mediated their chromatin remodeling during Th17 differentiation. Trim33 thus promotes the proinflammatory function of Th17 cells by inducing IL-17 and suppressing IL-10 expression.
UR - http://www.scopus.com/inward/record.url?scp=85054609351&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85054609351&partnerID=8YFLogxK
U2 - 10.1084/jem.20170779
DO - 10.1084/jem.20170779
M3 - Article
C2 - 29930104
AN - SCOPUS:85054609351
SN - 0022-1007
VL - 215
SP - 1853
EP - 1868
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -