Prostaglandin and prostacyclin regulation of Th1 responses [ptgir_ko]
Metabolic reprogramming is an integral component of normal Th1 induction and contraction. Whereas Th1 inducing signals are largely defined, the pathways underlying timely Th1 contraction remain poorly understood. Here, we show that a CD4+ T cell-intrinsic prostanoid lipid mediator production and signaling machinery, controlled by cell-autonomous complement C5, governs the Th1 shutdown program. Overall design: This was a three part study. First, human CD4 T cells were stimulated with anti-CD3+46 in the presence or absence of a C5AR double receptor antagonist and microarray analysis performed. Second, CD4 T cell from WT or PTGIR-/- mice were stimulated for 2 hours and bulk RNA-sequencing was performed. Third, human CD4 T cells were isolated, treated with PTGIR or PTGIS siRNA, stimulated with anti-CD3+46, and IFNG-IL10- (DN), IFNG+IL10- (IFNG) populations were sorted before RNA-sequencing.