Prostaglandin E₂-EP4 signaling promotes immune inflammation through T_H1 cell differentiation and T_H17 cell expansion

Chengcan et al. Nature Medicine 15, 633-640 (2009)

Speaker: 李建勳                                                  Time:14:00-15:00 10/07 2009

Commentator: 王志堯 老師                              Place: Room 601

Prostaglandin E₂ (PGE₂) was considered a suppressor of T_H1 cell differentiation through its specific G protein-coupled receptors, EP2 and EP4, but intriguingly, its immunosuppressive functions in vivo are rarely reported. In this study, the authors aim to reexamine the effects of PGE₂ on T cell subsets under different in vitro conditions and to investigate its roles in animal models in vivo. The first novel finding is that PGE₂ promotes T_H1 cell differentiation when naïve T cells are activated by stronger TCR stimulation and cultured under T_H1-skewing condition. In addition, PGE₂enhances IL-23-induced expansion of well-differentiated T_H17 cells. Both the effects of PGE₂ can be mediated through EP2 and EP4. The authors further reveal that PGE₂ also enhances IL-23 production from activated dendritic cells through EP4. In mouse models of experimental autoimmune encephalomyelitis and contact hypersensitivity, two diseases involving pathogenic T_H1 and T_H17 cells, EP4 antagonism decreases T cell proliferation and production of T_H1/T_H17 cytokines, resulting in suppression of the disease progression. Therefore, this study not only indicates that PGE₂ can facilitate development of T_H1 and T_H17 cells, but also suggests that manipulation of PGE₂ and its receptors is another potential therapeutic strategy for various immune diseases.

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