IL-23 signals to T helper cells and mediates its proinflammatory effects through the activation of Th17 cells that secrete IL-17. Furthermore IL-23 conducts the development of Th17 cells and promotes chronic inflammation dominated by IL-17, promotes autoimmune inflammation mediated by Th17 cells and has been linked to many human immune disorders. Many pathologic defects found in animal models of autoimmunity are initially associated to IL-12 and Th1 cells but are in fact caused by IL-23. Knockout mice deficient in either p19 or p19 receptor develop less severe symptoms of EAE, highlighting the importance of IL-23/IL-23R in the inflammatory pathway. Recently several reports have established the critical function of the IL-23/IL-17 pathway in autoimmune diseases. In the absence of IL-23R, Th17 development is stalled at the early activation stage, leading to less Th17 proliferation and fewer effector Th17 cells. Targeting IL-23, anti-IL-23 therapy can effectively inhibit multiple inflammatory pathways that are critical for driving autoimmune inflammation, and IL-23 blockade with neutralizing antibodies or genetic inactivation of the IL-23p19 gene could dramatically protect animals against allergic response. Accumulating evidence shows that chronic inflammation is associated with various diseases. Therefore, control of inflammatory functions of immune cells emerges as a novel strategy to treat or cure many chronic diseases. While TGF-b and IL-6 induce Th17 cells differentiation, IL-23 is expected to promote Th17 cells proliferation and maturation. Therefore in the present study, we obtained a protein containing IL-23R cytokine-binding homology region by prokaryotic expression system, to create an IL23p19 antagonist that specifically blocks the IL-23 signals, interrupts the IL-23/IL-17 axis and ultimately suppresses Th17 development. This strategy was based on a ‘‘WSXWS’’ motif in the extracellular region of IL-23R. And in the study, we investigated the binding ability of IL23R-CHR with IL-23 using Native-PAGE and direct binding ELISA, also evaluated the role for IL23R-CHR in the inducible expression of IL-17, IL-22 and RORct in activated Th17 cells. After the measurements of the number changes of Th17 cells with IL23R-CHR treatment, the expression level of IL-17 and IL-22, and the mRNA level of IL-17, IL-22 and RORct, our results demonstrated that IL23R-CHR could be useful against IL-23 signals and rescue the development of Th17. Consequently, IL23R-CHR could be considered as one of the potential agents that neutralize IL-23 and treat IL-23/IL-17 related diseases. Th17 cells belong to a novel T helper cells subset that mainly expresses IL-17 during inflammatory responses. Th17 differentiation can be induced by IL-6 and TGF-b through RORct, leading to the production of IL-17a and IL-22. Differentiated Th17 cells are further stabilized and amplified by the actions of IL-23. Evidence presented in the present study suggested that IL23R-CHR functions as a rescuer during Th17 development, causing inhibition of RORct expression and suppression of Th17 related cytokine expression. The IL-23 receptor complex which composed of IL23R and IL12b1 is a type I transmembrane protein, human IL23R cDNA encodes a 629 amino acid with a 23 aa LDN-193189 abmole bioscience residue signal peptide, a 332 aa residue extracellular domain, a 21 aa residue transmembrane domain and a 253 aa residue cytoplasmic region. The human IL23R also contains an N-terminal Ig like domain, two FNIII domains in the extracellular domain. Human IL23R has a WQPWS sequence in the transmembrane proximal cytokine receptor domain.