title: The impact of ATRA on shaping human myeloid cell responses to epithelial cell-derived stimuli and on T-lymphocyte polarization.
abstract: Vitamin A plays an essential role in the maintenance of gut homeostasis but its interplay with chemokines has not been explored so far. Using an in vitro model system we studied the effects of human colonic epithelial cells (Caco2, HT-29, and HCT116) derived inflammatory stimuli on monocyte-derived dendritic cells and macrophages. Unstimulated Caco2 and HT-29 cells secreted CCL19, CCL21, and CCL22 chemokines, which could attract dendritic cells and macrophages and induced CCR7 receptor up-regulation by retinoic-acid resulting in dendritic cell migration. The chemokines Mk, CXCL16, and CXCL7 were secreted by all the 3 cell lines tested, and upon stimulation by IL-1β or TNF-α this effect was inhibited by ATRA but had no impact on CXCL1, CXCL8, and CCL20 secretion in response to IL-1β. In the presence of ATRA the supernatants of these cells induced CD103 expression on monocyte-derived dendritic cells and when conditioned by ATRA and cocultured with CD4(+) T-lymphocytes they reduced the proportion of Th17 T-cells. However, in the macrophage-T-cell cocultures the number of these effector T-cells was increased. Thus cytokine-activated colonic epithelial cells trigger the secretion of distinct combinations of chemokines depending on the proinflammatory stimulus and are controlled by retinoic acid, which also governs dendritic cell and macrophage responses.
authors.affiliation: Department of Immunology, Medical Faculty, University of Debrecen, Debrecen 4032, Hungary ; INRA, Unité de Virologie et Immunologie Moléculaires, Jouy-en-Josas, France ; AgroParisTech, Jouy-en-Josas, France.
authors.forename: Arunima
authors.identifier: 0000-0001-9264-5823
authors.initials: A
authors.lastname: Chatterjee
authors.affiliation: Department of Immunology, Medical Faculty, University of Debrecen, Debrecen 4032, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Gogolak
authors.affiliation: AgroParisTech, Jouy-en-Josas, France ; INRA, UMR 1319 Micalis, Jouy-en-Josas, France.
authors.forename: Hervé M
authors.initials: HM
authors.lastname: Blottière
authors.affiliation: Department of Immunology, Medical Faculty, University of Debrecen, Debrecen 4032, Hungary.
authors.forename: Éva
authors.initials: É
authors.lastname: Rajnavölgyi
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018938:Caco-2 Cells; D002465:Cell Movement; D018925:Chemokines / Q000378:metabolism; D002633:Chemotaxis; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008213:Lymphocyte Activation; D008264:Macrophages / Q000166:cytology; D009000:Monocytes / Q000166:cytology; D022423:Myeloid Cells / Q000166:cytology*; D058504:Th17 Cells / Q000166:cytology*; D014212:Tretinoin / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018925:Chemokines; D020381:Interleukin-17; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D014212:Tretinoin