Selective enhancement of expansion and function of Th17 cells by sphingosine 1‐phosphate and its type I G protein‐coupled receptor

Abstract

S1P is a lysosphingolipid product of hematopoietic and innate immune cells, that regulates numerous T cell functions through its S1P1 receptors. We developed an S1P1/OTII double transgenic (DTG) mouse with high T cell expression of S1P1 and an ovalbumin peptide (OVA)-specific antigen receptor (TCR). CD4 T cells from DTG mice and OVA TCR single TG (STG) mice proliferated and generated cytokines in response to OVA, whereas S1P affected their migration and cytokine production more when they were derived form DTG than STG mice. S1P increased generation of IL-17 by suspensions of OVA-stimulated CD4 T cells from DTG mice significantly more than for those from STG mice. Mean percentage increases in IL-17 production for 10−9M, 10−8M and 10−7M S1P were 237, 249 and 184 for CD4 T cells from DTG mice and 152, 158 and 115 for those from STG mice. Thus the S1P-S1P1 axis of CD4 T cells not only enhances the cytokine generation by Th2 over Th1 cells, but also promotes the contributions of Th17 cells (Supported by NIH HL31809 to EJG).