Prostaglandin E2 amplifies IL-17 production by γδ T cells during barrier inflammation

Abstract

Interleukin-17 (IL-17)-producing γδ (γδ17) T cells are innate-like lymphocytes that contribute to protective anti-microbial responses but are also implicated in pathogenic inflammation at barrier sites. Understanding tissue-specific signals that regulate this subset is important to boost host defense mechanisms, but also to mitigate immunopathology. Here, we demonstrate that prostaglandin E₂ (PGE₂), a cyclooxygenase-dependent member of the eicosanoid family, directly enhances cytokine production by circulating and tissue-specific γδ17 T cells in vitro. Gain- and loss-of-function in vivo approaches further reveal that although provision of PGE₂ amplifies psoriasiform inflammation, ablation of host mPGES1-dependent PGE₂ synthesis is dispensable for cutaneous γδ17 T cell activation. By contrast, loss of endogenous PGE₂ production or depletion of the gut microbiota compromises intestinal γδ17 T cell responses and increases disease severity during experimental colitis. Together, our results demonstrate how a lipid mediator can synergize with tissue-specific signals to enhance innate lymphocyte production of IL-17 during barrier inflammation.

Keywords: IL-17; colitis; gut; inflammation; microbiota; psoriasiform inflammation; skin; γδT cells.