Retinoic acid-primed human dendritic cells inhibit Th9 cells and induce Th1/Th17 cell differentiation
Autor: | Vineet Ahuja, Ritika Rampal, Amit Awasthi |
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Rok vydání: | 2015 |
Předmět: |
0301 basic medicine
Cellular differentiation T cell Immunology Retinoic acid Tretinoin Biology Monocytes Transforming Growth Factor beta1 03 medical and health sciences chemistry.chemical_compound Keratolytic Agents medicine Immunology and Allergy Humans Interleukin 9 CD40 Interleukin-9 Cell Differentiation Cell Biology Dendritic Cells Th1 Cells Cell biology 030104 developmental biology P19 cell medicine.anatomical_structure chemistry Interleukin 12 biology.protein Cytokines Th17 Cells Caco-2 Cells medicine.drug |
Zdroj: | Journal of leukocyte biology. 100(1) |
ISSN: | 1938-3673 |
Popis: | 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. |
Databáze: | OpenAIRE |
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