title: Retinoic acid-primed human dendritic cells inhibit Th9 cells and induce Th1/Th17 cell differentiation.
abstract: All-trans-retinoic acid plays a central role in mucosal immunity, where it promotes its synthesis by up-regulating CD103 expression on dendritic cells, induces gut tropic (α4β7(+) and CCR9(+)) T cells, and inhibits Th1/Th17 differentiation. Recently, murine studies have highlighted the proinflammatory role of retinoic acid in maintaining inflammation under a variety of pathologic conditions. However, as a result of limited human data, we investigated the effect of retinoic acid on human dendritic cells and CD4(+) T cell responses in the presence of polarizing (Th1/Th9/Th17) and inflammatory (LPS-induced dendritic cells) conditions. We report a novel role of retinoic acid in an inflammatory setup, where retinoic acid-primed dendritic cells (retinoic acid-monocyte-derived dendritic cells) up-regulated CCR9(+)T cells, which were observed to express high levels of IFN-γ in the presence of Th1/Th17 conditions. Retinoic acid-monocyte-derived dendritic cells, under Th17 conditions, also favored the induction of IL-17(+) T cells. Furthermore, in the presence of TGF-β1 and IL-4, retinoic acid-monocyte-derived dendritic cells inhibited IL-9 and induced IFN-γ expression on T cells. Experiments with naïve CD4(+) T cells, activated in the presence of Th1/Th17 conditions and absence of DCs, indicated that retinoic acid inhibited IFN-γ and IL-17 expression on T cells. These data revealed that in the face of inflammatory conditions, retinoic acid, in contrast from its anti-inflammatory role, could maintain or aggravate the intestinal inflammation.
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India; and.
authors.forename: Ritika
authors.initials: R
authors.lastname: Rampal
authors.affiliation: Center for Human Microbial Ecology, Translational Health Science and Technology Institute, Faridabad, New Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Awasthi
authors.affiliation: Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India; and vins_ahuja@hotmail.com.
authors.forename: Vineet
authors.initials: V
authors.lastname: Ahuja
mesh_terms: D018938:Caco-2 Cells; D002454:Cell Differentiation / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D016906:Interleukin-9 / Q000037:antagonists & inhibitors / Q000276:immunology*; D007641:Keratolytic Agents / Q000494:pharmacology; D009000:Monocytes / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology; D058504:Th17 Cells / Q000166:cytology* / Q000276:immunology; D053773:Transforming Growth Factor beta1; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D016207:Cytokines; D016906:Interleukin-9; D007641:Keratolytic Agents; D053773:Transforming Growth Factor beta1; D014212:Tretinoin
keywords: CD103+ DCs; T effector cells; inflammation; proinflammatory