Harnessing prostaglandin E2 signaling to ameliorate autoimmunity.

Prostaglandin E 2 (PGE 2) plays different roles through the inflammation and resolution cycle, acting in both proinflammatory and anti-inflammatory capacities. Dysregulated PGE 2 production and signaling has been implicated in the progression and chronic nature of certain autoimmune diseases. PGE 2 is produced by and can directly affect both immune cell populations and cells within the target organ/tissue. Recent data indicate that PGE 2 plays a pivotal role in the resolution of inflammation. We hypothesize that enhancing PGE 2 signaling during the resolution phase of inflammation promotes tissue homeostasis, halts the inflammation cycle, and ameliorates certain autoimmune diseases. A better understanding of PGE 2 signaling is needed to realize the therapeutic potential of this pathway in modulating the inflammation cycle, promoting resolution, and restoring tissue homeostasis in settings of autoimmunity. The etiology of most autoimmune diseases remains unknown; however, shared among them is a disruption of immunoregulation. Prostaglandin lipid signaling molecules possess context-dependent immunoregulatory properties, making their role in autoimmunity difficult to decipher. For example, prostaglandin E 2 (PGE 2) can function as an immunosuppressive molecule as well as a proinflammatory mediator in different circumstances, contributing to the expansion and activation of T cell subsets associated with autoimmunity. Recently, PGE 2 was shown to play important roles in the resolution and post-resolution phases of inflammation, promoting return to tissue homeostasis. We propose that PGE 2 plays both proinflammatory and pro-resolutory roles in the etiology of autoimmunity, and that harnessing this signaling pathway during the resolution phase might help prevent autoimmune attack. [ABSTRACT FROM AUTHOR]