Retinoic acid-primed human dendritic cells inhibit Th9 cells and induce Th1/Th17 cell differentiation. 2016

Ritika Rampal, and Amit Awasthi, and Vineet Ahuja
Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India; and.

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.

UI MeSH Term Description Entries
D007641 Keratolytic Agents Agents that soften, separate, and cause desquamation of the cornified epithelium or horny layer of skin. They are used to expose mycelia of infecting fungi or to treat corns, warts, and certain other skin diseases. Desquamating Agents,Skin-Peeling Agents,Agents, Desquamating,Agents, Keratolytic,Agents, Skin-Peeling,Skin Peeling Agents
D009000 Monocytes Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. Monocyte
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D003713 Dendritic Cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as SKIN and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process ANTIGENS, and present them to T-CELLS, thereby stimulating CELL-MEDIATED IMMUNITY. They are different from the non-hematopoietic FOLLICULAR DENDRITIC CELLS, which have a similar morphology and immune system function, but with respect to humoral immunity (ANTIBODY PRODUCTION). Dendritic Cells, Interdigitating,Interdigitating Cells,Plasmacytoid Dendritic Cells,Veiled Cells,Dendritic Cells, Interstitial,Dendritic Cells, Plasmacytoid,Interdigitating Dendritic Cells,Interstitial Dendritic Cells,Cell, Dendritic,Cell, Interdigitating,Cell, Interdigitating Dendritic,Cell, Interstitial Dendritic,Cell, Plasmacytoid Dendritic,Cell, Veiled,Cells, Dendritic,Cells, Interdigitating,Cells, Interdigitating Dendritic,Cells, Interstitial Dendritic,Cells, Plasmacytoid Dendritic,Cells, Veiled,Dendritic Cell,Dendritic Cell, Interdigitating,Dendritic Cell, Interstitial,Dendritic Cell, Plasmacytoid,Interdigitating Cell,Interdigitating Dendritic Cell,Interstitial Dendritic Cell,Plasmacytoid Dendritic Cell,Veiled Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D014212 Tretinoin An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE). Retinoic Acid,Vitamin A Acid,Retin-A,Tretinoin Potassium Salt,Tretinoin Sodium Salt,Tretinoin Zinc Salt,Vesanoid,all-trans-Retinoic Acid,beta-all-trans-Retinoic Acid,trans-Retinoic Acid,Acid, Retinoic,Acid, Vitamin A,Acid, all-trans-Retinoic,Acid, beta-all-trans-Retinoic,Acid, trans-Retinoic,Potassium Salt, Tretinoin,Retin A,Salt, Tretinoin Potassium,Salt, Tretinoin Sodium,Salt, Tretinoin Zinc,Sodium Salt, Tretinoin,Zinc Salt, Tretinoin,all trans Retinoic Acid,beta all trans Retinoic Acid,trans Retinoic Acid
D016207 Cytokines Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. Cytokine
D016906 Interleukin-9 A multifunctional cytokine secreted by primarily by activated TH2 CELLS that may play a role as a regulator of allergic INFLAMMATION. It has been shown to enhance the growth and CELL DIFFERENTIATION of MAST CELLS, and can act on a variety of other immune cells. IL-9,P40 T-Cell Growth Factor,T-Cell Growth Factor P40,IL9,Interleukin 9,P40 T Cell Growth Factor,T Cell Growth Factor P40
D053773 Transforming Growth Factor beta1 A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME. TGF-beta1,Transforming Growth Factor-beta1,TGF-beta-1,TGF-beta1 Latency-Associated Protein,TGF-beta1LAP,Transforming Growth Factor beta 1 Latency Associated Peptide,Transforming Growth Factor beta I,Latency-Associated Protein, TGF-beta1,TGF beta 1,TGF beta1 Latency Associated Protein,TGF beta1LAP
D058504 Th17 Cells A subset of helper-effector T-lymphocytes which synthesize and secrete INTERLEUKINS IL-17; IL-17F; and IL-22. These cytokines are involved in host defenses and tissue inflammation in autoimmune diseases. T Helper 17 Cell,TH-17 Cell,Th17 Cell,Type 17 Helper T Cell,T Helper 17 Cells,TH-17 Cells,Type 17 Helper T Cells,Cell, TH-17,Cell, Th17,Cells, TH-17,Cells, Th17,TH 17 Cell,TH 17 Cells

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