Emerging roles of prostanoids in T cell-mediated immunity

Three distinct subsets of T helper (Th) cells, Th1, Th2, and Th17, not only contribute to host defense against pathogens, but also cause many types of immune diseases. Differentiation and functions of these T cell subsets are mainly regulated by specific cytokines. Intriguingly, recent studies have revealed that prostanoids including various types of prostaglandins (PGs) and thromboxane (TX) are also involved in these processes. Prostanoids exert their actions by binding to their specific receptors. They include PGD receptor, EP1, EP2, EP3, and EP4 subtypes of PGE receptor, PGF receptor, PGI receptor, and TX receptor. From many in vitro findings, prostanoids, especially PGE₂, were traditionally believed to be an immunosuppressant. However, studies using mice deficient in each type or subtype of prostanoid receptors and their selective agonists and antagonists have revealed that prostanoids collaborate with cytokines, and critically regulate T cell proliferation, differentiation and functions. Recent studies have revealed that PGE₂ facilitates Th1 cell differentiation and Th17 cell expansion in collaboration with IL-12 and IL-23, respectively, and that these PGE₂ actions contribute to development of immune diseases mediated by these Th subsets. Furthermore, studies using the receptor-deficient mice have also revealed that other prostanoids including PGD₂ and PGI₂ contribute to regulation of immune diseases of the Th2 type such as allergic asthma. These findings shed a new light on the roles of prostanoids in T cell-mediated immunity and immune diseases.