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Front. Immunol. | doi: 10.3389/fimmu.2018.02954

mPGES-1-mediated production of PGE2 and EP4 receptor sensing regulate T cell colonic inflammation

  • 1Vanderbilt University, United States
  • 2Vanderbilt University Medical Center, United States

PGE2 is a lipid mediator of the initiation and resolution phases of inflammation, as well as a regulator of immune system responses to inflammatory events. PGE2 is produced and sensed by T cells, and autocrine or paracrine PGE2 can affect T cell phenotype and function. In this study, we use a T cell-dependent model of colitis to evaluate the role of PGE2 on pathological outcome and T-cell phenotype. CD4+ T effector cells either deficient in mPGES-1 or the PGE2 receptor EP4 are less colitogenic. Absence of T cell autocrine mPGES1-dependent PGE2 reduces colitogenicity in association with an increase in CD4+RORgt+ cells in the lamina propria. In contrast, recipient mice deficient in mPGES-1 exhibit more severe colitis that corresponds with a reduced capacity to generate FoxP3+ T cells, especially in mesenteric lymph nodes. Thus our research defines how mPGES-1-driven production of PGE2 by different cell types in distinct intestinal locations impacts T cell function during colitis. We conclude that PGE2 has profound effects on T cell phenotype that are critically dependent on the microenvironment.

Keywords: IBD – Inflammatory bowel diseases, T cell, PGE2, Colitis, Th17 & Tregs cells, Inflammation Immunomodulation, Th17 activation, Treg = regulatory T cell

Received: 27 Jul 2018; Accepted: 30 Nov 2018.

Edited by:

Claudio Mauro, University of Birmingham, United Kingdom

Reviewed by:

Anne L. Astier, INSERM U1043 Centre de Physiopathologie de Toulouse Purpan, France
Mary A. Markiewicz, University of Kansas Medical Center, United States  

Copyright: © 2018 Maseda, Banerjee, Johnson, Washington, Kim, Lau and Crofford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Leslie J. Crofford, Vanderbilt University Medical Center, Nashville, Tennessee, United States, leslie.j.crofford@vanderbilt.edu