Prostaglandin E2 enhances Th17 responses by differentially modulating the production of IL-17 and IFN-g by purified memory CD4+ T cells.

NAPOLITANI G; ACOSTA RODRIGUEZ EV; LANZAVECCHIA A; SALLUSTO F

WILEY-V C H VERLAG GMBH

Año: 2009 vol. 39 p. 1301 - 1301

he contribution of Th1 and Th17 cells in chronic inflammatory conditions leading to autoimmunity remains highly controversial. In inflamed tissues, production of prostaglandins by COX-2 has been proposed to favor Th17 responses indirectly by increasing IL-23 and blocking IL-12 release from APC. We report here that prostaglandin E2 (PGE2) can directly modulate cytokine production by human memory CD41 T cells. TCR triggering in the presence of PGE2 increased IL-17 and reduced IFN-c production by freshly isolated memory T cells or T-cell clones. PGE2 triggered the EP2 and EP4 receptors expressed on T cells leading to a rapid increase of retinoic-acid-related orphan receptor-ct (ROR-ct) and decrease of T-cell-specific T-box transcription factor 21 (T-bet) mRNA. Moreover, PGE2 promoted the selective enrichment of IL-17-producing cells by differentially modulating the proliferation of memory T-cell subsets in vitro. Taken together our results indicate that T-cell effector functio