title: Protection against Th17 cells differentiation by an interleukin-23 receptor cytokine-binding homology region.
abstract: Th17 cells have been reported to produce proinflammatory cytokines like Interleukin-17, IL-22, and regarded as important players in various inflammatory diseases. One of the IL-12 cytokine family cytokines, IL-23, composed of p19 and p40 subunit, is known for its potential to promote Th17 development and IL-17 producing, and the IL-23/IL-17 pathway is considered to be potential therapeutic target for autoimmune inflammation responses. Knockout mice deficient in either IL-23 or IL-17 related genes can suppress the allergic responses. Several IL-23 or IL-17 neutralizing agents are being evaluated in vitro or in vivo to disrupt the IL-23/IL-17 axis. Herein, we report that prokaryotically expressed soluble IL-23 receptor cytokine-binding homology region as an endogenous extracellular receptor analogue could be a natural antagonist against IL-23/IL-17 axis. We provide evidence that IL23R-CHR can bind to IL-23 in a dose-dependent manner in vitro, and block IL-23 signal by IL23R-CHR reducing the RORγt expression, which in turn lowers the expression of IL-17/IL-22, thus protecting naive CD4+ T cells against Th17 development. Together, this study indicates the importance of IL-23 pathway in Th17 development and the negative regulation of Th17 development by IL23R-CHR, and highlights the important roles of the soluble receptor extracellular region in the therapeutic strategy of neutralizing IL-23.
authors.affiliation: State Key Laboratory of Natural Medicines, School of Life Science and Technology, China Pharmaceutical University, Nanjing, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Cheng
authors.initials: C
authors.lastname: Luo
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhu
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Xiangdong
authors.initials: X
authors.lastname: Gao
authors.forename: Wenbing
authors.initials: W
authors.lastname: Yao
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000378:metabolism / Q000502:physiology*; D058504:Th17 Cells / Q000166:cytology*
chemical_list: D016207:Cytokines; C515500:IL23R protein, human; D018123:Receptors, Interleukin