Prostaglandins differentially modulate mucosal associated invariant T cell activation and function according to stimulus.
Mehta H., Tasin I., Hackstein CP., Willberg C., Klenerman P.
Mucosal Associated Invariant T (MAIT) cells are an innate-like T cell type conserved in many mammals and especially abundant in humans. Their semi-invariant T cell receptor (TCR) recognises the MHC-like molecule MR1 presenting riboflavin intermediates associated with microbial metabolism. Full MAIT cell triggering requires co-stimulation via cytokines, and the cells can also be effectively triggered in a TCR-independent manner by cytokines (e.g. IL-12 and IL-18 in combination). Thus, triggering of MAIT cells is highly sensitive to local soluble mediators. Suppression of MAIT cell activation has not been well explored and could be very relevant to their roles in infection, inflammation, and cancer. Prostaglandins are major local mediators of these micro-environments which can have regulatory roles for T cells. Here, we explored whether prostaglandins suppressed MAIT cell activation in response to TCR-dependent and -independent signals. We found that PGE2 and to a lesser extent PGD2 , but not leukotrienes, suppressed MAIT cell responses to E. coli or TCR triggers. However, there was no impact on cytokine induced triggering. The inhibition was blocked by targeting the signalling mediated via PTGER2 and PTGER4 receptors in combination. These data indicate that prostaglandins can potentially modulate local MAIT cell functions in vivo and indicate distinct regulation of the TCR-dependent and -independent pathways of MAIT cell activation.