title: Prostaglandin E2 and IL-23 plus IL-1β differentially regulate the Th1/Th17 immune response of human CD161(+) CD4(+) memory T cells.
abstract: 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.
authors: Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA. amb145@pitt.edu
authors: Arthur
authors: A
authors: Barrie
authors: Anupriya
authors: A
authors: Khare
authors: Matthew
authors: M
authors: Henkel
authors: Yingze
authors: Y
authors: Zhang
authors: M Michael
authors: MM
authors: Barmada
authors: Richard
authors: R
authors: Duerr
authors: Anuradha
authors: A
authors: Ray
mesh_terms: D015704:CD4 Antigens / Q000378:metabolism; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D039441:Integrin alpha4 / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000494:pharmacology*; D053759:Interleukin-23 / Q000494:pharmacology*; D055651:NK Cell Lectin-Like Receptor Subfamily B / Q000378:metabolism*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
chemical_list: D015704:CD4 Antigens; D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D055651:NK Cell Lectin-Like Receptor Subfamily B; D039441:Integrin alpha4; D007371:Interferon-gamma; D015232:Dinoprostone