TY - JOUR
T1 - Interleukin-17C Promotes Th17 Cell Responses and Autoimmune Disease via Interleukin-17 Receptor E
AU - Chang, Seon Hee
AU - Reynolds, Joseph M.
AU - Pappu, Bhanu P.
AU - Chen, Guangjie
AU - Martinez, Gustavo J.
AU - Dong, Chen
N1 - Funding Information:
We thank MD Anderson Genetic Engineering Mouse Facility for their assistance in generation of Il17c gene-targeted animals, K. Murphy for RV-GFP vector, D. Littman for the CD4 minigene construct, and the C.D. lab members for their help. The work is supported by research grants from NIH (to C.D.). J.M.R. receives an NCI training grant and C.D. receives a Research Trust Fellowship, is Olga and Harry Wiess Distinguished University Chair in Cancer Research of the University of Texas MD Anderson Cancer Center, and is a Leukemia and Lymphoma Society Scholar.
PY - 2011/10/28
Y1 - 2011/10/28
N2 - Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show that an IL-17 cytokine family member, IL-17C, was induced in a Th17 cell-dependent autoimmune disease and was required for its pathogenesis. IL-17C bound to IL-17RE, a member of IL-17 receptor family whose full-length isoform was selectively expressed in Th17 cells and signaled via an IL-17RA-RE receptor complex and the downstream adaptor Act1. IL-17C-IL-17RE induced the expression of a nuclear IkappaB family member, IκBζ, in Th17 cells to potentiate the Th17 cell response. Thus, our work has identified a cytokine-receptor pair with important function in regulating proinflammatory responses. This pathway may be targeted to treat autoimmune diseases.
AB - Although several interleukin-17 (IL-17) family members and their receptors have been recently appreciated as important regulators in inflammatory diseases, the function of other IL-17 cytokines and IL-17 receptor-like molecules is unclear. Here we show that an IL-17 cytokine family member, IL-17C, was induced in a Th17 cell-dependent autoimmune disease and was required for its pathogenesis. IL-17C bound to IL-17RE, a member of IL-17 receptor family whose full-length isoform was selectively expressed in Th17 cells and signaled via an IL-17RA-RE receptor complex and the downstream adaptor Act1. IL-17C-IL-17RE induced the expression of a nuclear IkappaB family member, IκBζ, in Th17 cells to potentiate the Th17 cell response. Thus, our work has identified a cytokine-receptor pair with important function in regulating proinflammatory responses. This pathway may be targeted to treat autoimmune diseases.
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U2 - 10.1016/j.immuni.2011.09.010
DO - 10.1016/j.immuni.2011.09.010
M3 - Article
C2 - 21982598
AN - SCOPUS:80755133721
SN - 1074-7613
VL - 35
SP - 611
EP - 621
JO - Immunity
JF - Immunity
IS - 4
ER -