The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo 

McGeachy, M.J. et al. 2009. Nat. Immunol. 10, 314–324.

Speaker: Chia-Chun Tsia (蔡佳純)                         Time: 15:00~16:00, Apr. 15, 2009

Commentator: Dr. Yee-Shin Lin (林以行老師)               Place: Room 601

Abstract:

        Interleukin  17-producing helper T cells (T_H17 cells) play a pathogenic role in autoimmune and inflammatory diseases. Previous in vitro studies  have shown that interleukin 23 (IL-23), a cytokine that consists of p19 and p40 subunits, serves an essential function in T_H17-mediated pathogenesis¹. However, the mechanisms of how IL-23 signaling regulates T_H17 cells in vivo have not been addressed so far. Recently, IL-23 receptor gene has been identified as a susceptibility gene for human inflammatory bowel disease by the genome-wide screening².Therefore, the authors used IL-23 receptor deficient (Il23ra^-/-) and mixed bonemarrow chimeric mice to investigate the role of IL-23 signaling in experimental autoimmune encephalomyelitis model. They found that Il23ra^-/- mice were resistant to the induction of experimental autoimmune encephalomyelitis that confirmed that this receptor was required for IL-23 signaling in vivo. They also detected the expression of cell markers in T_H17 cells by OT-II tracking system to address whether IL-23 signaling regulated the differentiation of T_H17 cells. They found that T_H17 cells showed an immature phenotype which failed to maintain IL-17 production in the absence of IL-23 signaling. The results indicated IL-23 signaling  was a crucial factor in T_H17 cell development, especially in the late stage of T_H17 cell differentiation. In addition, they used a T_H1-dependent model (Toxoplasma gondii infection) to investigate the relationship between IL-23 signaling and T_H1 response. They demonstrated that T_H1 cell response was IL-23 independent. Besides, they also proved that the impaired proliferation of effector T_H17 cells in the lymph nodes resulted in fewer T_H17 cells homing toward the peripheral tissues and bloodstream. This study shows that IL-23 receptor regulates the terminal differentiation of T_H17 cells and it is tightly associated with T_H17 cell-mediated pathogenesis. It implicates that targeting IL-23 receptor as therapeutic strategies in T_H17 cell-mediated diseases in humans may be practical.

References:

11.            Langrish, C.L. et al. 2005. IL-23 drives a pathogenic T cell population that induces

 autoimmune inflammation. J. Exp. Med. 201, 233-240.

2.   Duerr, R.H. et al. 2006. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314, 1461-1463.