We examined how the absence of PAF receptor signaling (PTAFR-/-) or excessive PAF receptor activation (PLA2G7-/-) affects DSS-mediated colitis in vivo and T cell activation by a-CD3/a-CD28 in vitro. The inflammatory response in the colon and in in vitroactivated cells was assessed by quantifying cytokine gene expression by real time PCR..
In WT mice treatment with DSS leads to an increase in cytokines characteristic for the TH17-response, while in PTAFR-/- mice we observed a complete absence of IL17 and IL22. The TH17-specific chemokine CCL20 and the TH17-specific chemokine receptor CCR6 were significantly increased in the colons of PLA2G7-/- mice, and they were significantly decreased in colons of PTAFR-/- mice, as compared to wild type (WT) colons. In vitro stimulated T cells showed a non-polarized increase in cytokine transcipts in PLA2G7-/- and a non-polarized decrease in PTAFR-/-, as compared to WT. .
Our results suggest that signaling through PAF receptor is required for maximal non-polarized T cell activation in vitro and for a maximal TH17-type polarized response in the colon in vivo. This is best explained by a role for PAF in TH17-specific homing to the intestine and not by selective activation of TH17 cells. A precise delineation of PAF-specific mechanisms in the polarity of T cell-mediated inflammatory response may lead to novel treatment strategies for IBD.