Two distinct helper T (TH) subsets, TH1 and T H17, mediate tissue damage and inflammation in animal models of various immune diseases such as multiple sclerosis, rheumatoid arthritis, inflammatory bowel diseases and allergic skin disorders. These experimental findings, and the implication of these T H subsets in human diseases, suggest the need for pharmacological measures to manipulate these T H subsets. Here we show that prostaglandin E2 (PGE2) acting on its receptor EP4 on T cells and dendritic cells not only facilitates TH1 cell differentiation but also amplifies interleukin-23-mediated TH17 cell expansion in vitro. Administration of an EP4-selective antagonist in vivo decreases accumulation of both TH1 and TH17 cells in regional lymph nodes and suppresses the disease progression in mice subjected to experimental autoimmune encephalomyelitis or contact hypersensitivity. Thus, PGE 2-EP4 signaling promotes immune inflammation through T H1 differentiation and TH17 expansion, and EP4 antagonism may be therapeutically useful for various immune diseases.
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)