Prostaglandin I2 regulates IL-17 production by invariant natural killer T cells (108.7)

Abstract

Abstract PGI2 is an immunoregulatory prostanoid that is known to limit allergic inflammation. Our previous studies have shown that the PGI2 receptor, IP, also plays an important role in the development of IL-17-producing γδ T cells. Using mice lacking the PGI2 receptor (IPKO), we have investigated whether PGI2 is required for programming invariant natural killer T cells (iNKT) to produce IL-17. The GalCer response of spleen cells from the IPKO mouse was markedly reduced compared to wild type (WT) control animals. Paradoxically, the IL-17 production elicited by iNKT cells isolated from the lungs of IPKO mice stimulated with GalCer was 1.7-5.7 fold elevated over WT control animals. The elevated GalCer response in IPKO lungs was not associated with an increase in CD1d expression or the number of CD4+NK1.1+ or CD4+DX5+ iNKT cells in the lung. The exposure of IPKO animals to 1.5 ppm O3 resulted in a further increase in IL-17 production by lung mononuclear cells (LMC) in response to GalCer. These observations are consistent with iNKT responses being limited by a suppressive mechanism operative in the WT, but not IPKO lung tissue. The regulatory cells were not γδ T cells since the IL-17 produced by LMC in mice lacking the δ TCR chain remained low. Collectively, these results demonstrate that the GalCer response in normal lungs is depressed by a PGI2 dependent mechanism. The role for PGI2 in promoting the regulation of iNKT cells by regulatory cells, including CD4+ nTreg will be discussed.