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

Abstract

Interleukin-17 (IL-17)-producing gd (gd17) 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 E 2 (PGE 2 ), a cyclooxygenase-dependent member of the eicosanoid family, directly enhances cytokine production by circulating and tissue-specific gd17 T cells in vitro. Gain-and loss-of-function in vivo approaches further reveal that although provision of PGE 2 amplifies psoriasiform inflammation, ablation of host mPGES1-dependent PGE 2 synthesis is dispensable for cutaneous gd17 T cell activation. By contrast, loss of endogenous PGE 2 production or depletion of the gut microbiota compromises intestinal gd17 T cell responses and increases disease severity during experimental colitis. Together, our results demonstrate how a lipid mediator can synergize with tissuespecific signals to enhance innate lymphocyte production of IL-17 during barrier inflammation.

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