Prostaglandin signaling promotes neuroinflamation

 

Opposite to previously reported results, Yao and colleagues demonstrate that prostaglandin E2 (PGE2) engages the EP2 and EP4 receptors on T lymphocytes and dendritic cells to promote in vitro the differentiation and expansion of Th1 and Th17 helper T-cells. Both lineages participate in the development of experimental and human autoimmunity. Th1 differentiation appears to be mediated by PI3K signaling whereas Th17 is mediated by cAMP and augmentation of IL-23 production. Selective EP4 receptor antagonism in vivo decreases their accumulation in regional lymph nodes and inhibits disease progression in EAE mice. This was unexpected given the redundant actions of EP2 and EP4. The authors propose EP4 as a candidate drug target for immunomodulation of autoimmune disorders including multiple sclerosis (Nat Med 2009;doi:10.1038/nm.1968).

Opposite to previously reported results, Yao and colleagues demonstrate that prostaglandin E2 (PGE2) engages the EP2 and EP4 receptors on T lymphocytes and dendritic cells to promote in vitro the differentiation and expansion of Th1 and Th17 helper T-cells. Both lineages participate in the development of experimental and human autoimmunity. Th1 differentiation appears to be mediated by PI3K signaling whereas Th17 is mediated by cAMP and augmentation of IL-23 production. Selective EP4 receptor antagonism in vivo decreases their accumulation in regional lymph nodes and inhibits disease progression in EAE mice. This was unexpected given the redundant actions of EP2 and EP4. The authors propose EP4 as a candidate drug target for immunomodulation of autoimmune disorders including multiple sclerosis (Nat Med 2009;doi:10.1038/nm.1968).