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      Impact of Retinoic Acid on Immune Cells and Inflammatory Diseases

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          Abstract

          Vitamin A metabolite retinoic acid (RA) plays important roles in cell growth, differentiation, organogenesis, and reproduction and a key role in mucosal immune responses. RA promotes dendritic cells to express CD103 and to produce RA, enhances the differentiation of Foxp3 + inducible regulatory T cells, and induces gut-homing specificity in T cells. Although vitamin A is crucial for maintaining homeostasis at the intestinal barrier and equilibrating immunity and tolerance, including gut dysbiosis, retinoids perform a wide variety of functions in many settings, such as the central nervous system, skin aging, allergic airway diseases, cancer prevention and therapy, and metabolic diseases. The mechanism of RA is interesting to explore as both a mucosal adjuvant and a combination therapy with other effective agents. Here, we review the effect of RA on innate and adaptive immunity with a special emphasis on inflammatory status.

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          Most cited references150

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          Up on the tightrope: natural killer cell activation and inhibition.

          Natural killer (NK) cells circulate through the blood, lymphatics and tissues, on patrol for the presence of transformed or pathogen-infected cells. As almost all NK cell receptors bind to host-encoded ligands, signals are constantly being transmitted into NK cells, whether they interact with normal or abnormal cells. The sophisticated repertoire of activating and inhibitory receptors that has evolved to regulate NK cell activity ensures that NK cells protect hosts against pathogens, yet prevents deleterious NK cell-driven autoimmune responses. Here I highlight recent advances in our understanding of the structural properties and signaling pathways of the inhibitory and activating NK cell receptors, with a particular focus on the ITAM-dependent activating receptors, the NKG2D-DAP10 receptor complexes and the CD244 receptor system.
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            Skin immune sentinels in health and disease.

            Human skin and its immune cells provide essential protection of the human body from injury and infection. Recent studies reinforce the importance of keratinocytes as sensors of danger through alert systems such as the inflammasome. In addition, newly identified CD103(+) dendritic cells are strategically positioned for cross-presentation of skin-tropic pathogens and accumulating data highlight a key role of tissue-resident rather than circulating T cells in skin homeostasis and pathology. This Review focuses on recent progress in dissecting the functional role of skin immune cells in skin disease.
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              Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells.

              Normal intestinal mucosa contains abundant immunoglobulin A (IgA)-secreting cells, which are generated from B cells in gut-associated lymphoid tissues (GALT). We show that dendritic cells (DC) from GALT induce T cell-independent expression of IgA and gut-homing receptors on B cells. GALT-DC-derived retinoic acid (RA) alone conferred gut tropism but could not promote IgA secretion. However, RA potently synergized with GALT-DC-derived interleukin-6 (IL-6) or IL-5 to induce IgA secretion. Consequently, mice deficient in the RA precursor vitamin A lacked IgA-secreting cells in the small intestine. Thus, GALT-DC shape mucosal immunity by modulating B cell migration and effector activity through synergistically acting mediators.
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                Author and article information

                Contributors
                Journal
                Mediators Inflamm
                Mediators Inflamm
                MI
                Mediators of Inflammation
                Hindawi
                0962-9351
                1466-1861
                2018
                9 August 2018
                : 2018
                : 3067126
                Affiliations
                Laboratory of Dermatology and Immunodeficiencies, LIM-56, Department of Dermatology, School of Medicine, University of São Paulo, Institute of Tropical Medicine of São Paulo, São Paulo, SP, Brazil
                Author notes

                Academic Editor: Naïma Moustaïd-Moussa

                Author information
                http://orcid.org/0000-0002-5546-1977
                http://orcid.org/0000-0001-5622-903X
                http://orcid.org/0000-0002-7911-1824
                Article
                10.1155/2018/3067126
                6109577
                30158832
                8926bc74-bd9d-4781-9ffd-ddf831d665df
                Copyright © 2018 Luana de Mendonça Oliveira et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 March 2018
                : 16 June 2018
                : 28 June 2018
                Funding
                Funded by: Universidade de São Paulo
                Funded by: Fundação de Amparo à Pesquisa do Estado de São Paulo
                Categories
                Review Article

                Immunology
                Immunology

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