Regulation of IL-9 expression by IL-25 signaling

Pornpimon, A. et al 2010 Nat. Immunology 11, 250-256

Speaker: Jhih-Sin Lu (陸致信)                              Time: 13:00~14:00,May.26, 2010

Commentator: Dr. Huan-Yao Lei(黎煥耀老師)   Place: Room 601

Abstract:

Interleukin-9 (IL-9) was classified in T_H2 cytokine and corrected with clinical observation or animal model of asthma or parasite disease. The regulation of IL-9 expression had been demonstrated to distinct from other classical T_H2 cytokines such IL-4 IL-5 and IL-13. IL-25 had been referred to regulate IL-9, other T_H2 cytokines and IL-17 receptor A/B (IL-17RA/RB) expression in mice model. The IL-17RA and RB are essential for IL-25 signaling on T cells¹, but how IL-25 to regulate IL-9 expression is need to be defined. In recent study, Dardalhon, V. et al and Veldhoen, M. et al reported in the present of IL-4 and TGF-β naïve T cell differentiated a T_H2-like subset: T_H9, which expressed more IL-9 than T_H2 cell^2,3. Based on previous study in T_H2 cell, author hypothesized that T_H9 cell could be regulated by IL-25 and the up-regulated IL-9 expression is dependent on IL-25 signaling in allergic lung disease. In this study author found that IL-17RB had been up-regulated not only on T_H2 but T_H9 cell, and T_H9 expressed more IL-9 than T_H2 cell. Consistent with previous study, IL-17RA/RB is essential for IL-25 signaling and IL-9 induction. Otherwise, IL-9 expression induced by enhancing IL-17RB signaling that required TGF-β in vivo. This data demonstrated IL-25 expression is necessary for IL-9 expression in allergic lung disease. The regulation of IL-9 also implied that the existence of a new lineage of T cell.

References:

1. Erika A. Rickel et al Identification of function roles for both IL-17RAB and IL-17RA in mediating IL-25-induced activities. J. Immunol. 181, 4299-4310 (2008)

2. Dardalhon, V. et al. IL-4 inhibits TGF-beta-induced Foxp3+ T cells and, together with TGF-beta, generates IL-9+ IL-10+ Foxp3− effector T cells. Nat. Immunol. 9, 1347–1355 (2008).

3. Veldhoen, M. et al. Transforming growth factor-beta ‘reprograms’ the differentiation of T helper 2 cells and promotes an interleukin 9-producing subset. Nat. Immunol. 9, 1341–1346 (2008).