Open AccessProstaglandin E2 and IL‐23 plus IL‐1β Differentially Regulate the Th1/Th17 Immune Response of Human CD161 + CD4 + Memory T Cells
Author(s) -
Barrie Arthur,
Khare Anupriya,
Henkel Matthew,
Zhang Yingze,
Barmada M. Michael,
Duerr Richard,
Ray Anuradha
Publication year - 2011
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/j.1752-8062.2011.00300.x
Subject(s) - immune system , prostaglandin e2 , interleukin , immunology , prostaglandin e , cytokine , medicine , neuroscience , endocrinology , biology
Prostaglandin E2 (PGE2), interleukin (IL)‐23, and IL‐1beta (β) propagate inflammatory bowel disease (IBD) by enhancing the development and function of IL‐17 producing CD4 + T helper (Th17) cells. CD4 + T cells that express the C‐type lectin‐like receptor CD161 have been proposed to be the physiologic pool of circulating Th17 cells implicated in IBD. We sought to understand how PGE2, alone and in combination with IL‐23 and IL‐1β, modulate human peripheral CD161 + CD4 + memory T cells. We found that CD161 + cells comprise a significant proportion of human peripheral CD4 + memory T cells. PGE2 and IL‐23 plus IL‐1β synergistically induced early IL‐17A secretion from CD161 + CD4 + memory T cells and the selective enrichment of IL‐17A + CD161 + CD4 + memory T cells in culture. Conversely, IL‐23 plus IL‐1β partially opposed the PGE2‐mediated repression of early interferon gamma (IFN‐γ) secretion from CD161 + cells, as well as the PGE2‐mediated depletion of IFN‐γ + CD161 + cells. Our results suggest that PGE2 and IL‐23 plus IL‐1β induce the Th17 immune response preferentially in CD161 + CD4 + memory T cells, while divergently regulating their ability to express IFN‐γ. We hypothesize that Th17‐mediated chronic inflammation in IBD depends on the net response of CD161 + CD4 + memory T cells to both PGE2 and IL‐23 plus IL‐1β. Clin Trans Sci 2011; Volume 4: 268–273