, a bio/informatics shared resource is still "open for business" - Visit the CDS website


mPGES1-Dependent Prostaglandin E (PGE) Controls Antigen-Specific Th17 and Th1 Responses by Regulating T Autocrine and Paracrine PGE Production.

Maseda D, Johnson EM, Nyhoff LE, Baron B, Kojima F, Wilhelm AJ, Ward MR, Woodward JG, Brand DD, Crofford LJ
J Immunol. 2018 200 (2): 725-736

PMID: 29237778 · PMCID: PMC5760456 · DOI:10.4049/jimmunol.1601808

The integration of inflammatory signals is paramount in controlling the intensity and duration of immune responses. Eicosanoids, particularly PGE, are critical molecules in the initiation and resolution of inflammation and in the transition from innate to acquired immune responses. Microsomal PGE synthase 1 (mPGES1) is an integral membrane enzyme whose regulated expression controls PGE levels and is highly expressed at sites of inflammation. PGE is also associated with modulation of autoimmunity through altering the IL-23/IL-17 axis and regulatory T cell (Treg) development. During a type II collagen-CFA immunization response, lack of mPGES1 impaired the numbers of CD4 regulatory (Treg) and Th17 cells in the draining lymph nodes. Ag-experienced mPGES1 CD4 cells showed impaired IL-17A, IFN-γ, and IL-6 production when rechallenged ex vivo with their cognate Ag compared with their wild-type counterparts. Additionally, production of PGE by cocultured APCs synergized with that of Ag-experienced CD4 T cells, with mPGES1 competence in the APC compartment enhancing CD4 IL-17A and IFN-γ responses. However, in contrast with CD4 cells that were Ag primed in vivo, exogenous PGE inhibited proliferation and skewed IL-17A to IFN-γ production under Th17 polarization of naive T cells in vitro. We conclude that mPGES1 is necessary in vivo to mount optimal Treg and Th17 responses during an Ag-driven primary immune response. Furthermore, we uncover a coordination of autocrine and paracrine mPGES1-driven PGE production that impacts effector T cell IL-17A and IFN-γ responses.

Copyright © 2018 by The American Association of Immunologists, Inc.

MeSH Terms (16)

Animals Autocrine Communication Dinoprostone Epitopes, T-Lymphocyte Gene Expression Regulation Immunization Immunomodulation Lymphocyte Activation Mice Paracrine Communication Phenotype Prostaglandin-E Synthases Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype Th1 Cells Th17 Cells

Connections (1)

This publication is referenced by other Labnodes entities:

Links