Prostaglandin E2 amplifies IL-17 production by γδ T cells during barrier inflammation
Barbara Polese,
Bavanitha Thurairajah,
Hualin Zhang,
Cindy Leung Soo,
Clara A. McMahon,
Ghislaine Fontes,
Sabah N.A. Hussain,
Valerie Abadie,
Irah L. King
Affiliations
Barbara Polese
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Bavanitha Thurairajah
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Hualin Zhang
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Cindy Leung Soo
McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Clara A. McMahon
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Ghislaine Fontes
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada
Sabah N.A. Hussain
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada
Valerie Abadie
Section of Gastroenterology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
Irah L. King
Meakins-Christie Laboratories, Department of Medicine, McGill University Health Centre, Montreal, QC H4A 3J1, Canada; McGill Interdisciplinary Initiative in Infection and Immunity, Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada; Corresponding author
Summary: 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.
