Vitamin A and retinoic acid in T cell-related immunity
ABSTRACT Interest in vitamin A as a regulator of immune function goes back to the early 1900s. Recently, several lines of evidence have converged to show that retinoic acid (RA), a major oxidative metabolite of vitamin A, plays a key role in the differentiation of T cell subsets, the migration of T cells into tissues, and the proper development of T cell-dependent antibody responses. This review discusses evidence from experimental studies that RA promotes the differentiation of regulatory T cells, which help to suppress inflammatory reactions, and plays a significant role in normal mucosal immunity by modulating T cell activation and regulating cell trafficking. RA also promotes antibody responses to T cell-dependent antigens. Conversely, in a state of vitamin A deficiency, inflammatory T cell reactions may be inadequately opposed and therefore become dominant. Although data from human studies are still needed, the framework now developed from studies in mice and rat models suggests that adequate vitamin A status, whether derived from ingestion of preformed retinol or β-carotene, is important for maintaining a proper balance of well-regulated T cell functions and for preventing excessive or prolonged inflammatory reactions.
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ABSTRACT: Recent evidence have proposed that Tretinoin produced in the gut preferentially promote differentiation of FoxP3+Treg cells but inhibits Th17 lymphocytes, and this may be the main immunomdulatory mechanism of Tretinoin in vivo. This study was done to investigate the effects of Tretinoin in outbred white mice after challenge with sheep red blood cells (SRBC). Twenty male NMRI-mice randomly allocated in two equal groups. Mice were treated with 1×10(9) SRBCs emulsified in CFA intraperitoneally twice with one weak interval. Animals were bled 5 days after last injection. Moreover, 48 hr before bleeding time, 1×10(9) SRBCs were injected into the left hind foot pad of mice. Tretinoin (25 mg/kg-every other day) were intraperitoneally injected into the treatment group from the beginning of the study and continued throughout the study. The levels of anti-SRBC antibody and the specific cellular immune responses were measured by microhemagglutination test and footpad thickness, respectively. Moreover, splenocytes were checked for proliferation rate, respiratory burst, cytokine production and FoxP3+Treg cells frequency. Tretinoin markedly alleviated cellular immunity and concurrently potentiated humoral immunity after mice challenge with SRBCs. Furthermore, aside from reducing NBT reduction and lymphocyte proliferation, Tretinoin markedly suppressed the secretion of interleukin-17 and conversely, increased the production of interleukin-10. However, the level of IFN-γ and the frequency of FoxP3+Treg cells did not alter significantly. The in vivo immunomudlatoty effects of Tretinoin may be partly due to immune deviation from pro-inflammatory cytokine interleukin-17 to anti-inflammatory cytokine interleukin-10, but not absolutely depend on the expansion of FoxP3(+)Treg cells.Iranian Journal of Basic Medical Sciences 09/2014; 17(9):632-7. · 0.60 Impact Factor
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ABSTRACT: Vitamin A or retinol which is the natural precursor of several biologically active metabolites can be considered the most multifunctional vitamin in mammals. Its deficiency is currently, along with protein malnutrition, the most serious and common nutritional disorder worldwide. It is necessary for normal embryonic development and postnatal tissue homeostasis, and exerts important effects on cell proliferation, differentiation and apoptosis. These actions are produced mainly by regulating the expression of a variety of proteins through transcriptional and non-transcriptional mechanisms. Extracellular matrix proteins are among those whose synthesis is known to be modulated by vitamin A. Retinoic acid, the main biologically active form of vitamin A, influences the expression of collagens, laminins, entactin, fibronectin, elastin and proteoglycans, which are the major components of the extracellular matrix. Consequently, the structure and macromolecular composition of this extracellular compartment is profoundly altered as a result of vitamin A deficiency. As cell behavior, differentiation and apoptosis, and tissue mechanics are influenced by the extracellular matrix, its modifications potentially compromise organ function and may lead to disease. This review focuses on the effects of lack of vitamin A in the extracellular matrix of several organs and discusses possible molecular mechanisms and pathologic implications.Nutrients 11/2014; 6(11):4984-5017. DOI:10.3390/nu6114984 · 3.15 Impact Factor
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ABSTRACT: Members of the ALDH1 protein family, known as retinal dehydrogenases (RALDH), produce retinoic acid (RA), a metabolite of vitamin A, and may also oxidize other lipid aldehydes. Of three related ALDH1 genes, ALDH1A1 is most highly expressed in liver. ALDH1A1 is also rapidly gaining importance as a stem cell marker. We hypothesized that ALDH1A1 may have a broad cellular distribution in the liver, and that its expression may be regulated by RA and perturbed by inflammation. Studies were conducted in vitamin A-deficient and -adequate rats that were further treated with all-trans-RA or lipopolysaccharide (LPS) to induce a state of moderate inflammation. RALDH1A1 expression was determined by quantitative PCR and RALDH1, as well as marker gene expression, was determined by immunocytochemical methods. Inflammation reduced ALDH1A1 mRNA in whole liver regardless of the level of vitamin A in the diet (P < 0.05), while treatment with RA reduced ALDH1A1 expression only in chow-fed rats. ALDH1A1 protein exhibited diffuse staining in hepatocytes, with greater intensity in the periportal region including surrounding bile ducts. Six h after administration of LPS, portal region macrophages were more numerous and some of these cells contained ALDH1A1. Vimentin, which was used as a marker for stellate cells and fibroblasts, was increased by LPS, P = 0.011 vs. without LPS, in both ED1 (CD68)-positive macrophages and fibroblastic stellate-like cells in the parenchyma as well as portal regions. Alpha-smooth muscle actin staining was intense around blood vessels, but did not change after LPS or RA, nor overlap with staining for vimentin. Acute inflammation rapidly downregulates ALDH1A1 expression in whole liver while increasing its expression in periportal macrophages. Changes in ALDH1A1 expression appear to be part of the early acute-phase inflammatory response, which has been shown to alter the expression of other retinoid homeostatic genes. In addition, the rapid strong response of vimentin expression after treatment with LPS suggests that increased vimentin may be a useful marker of early hepatic inflammation.Nutrition & Metabolism 11/2014; 11:54. DOI:10.1186/1743-7075-11-54 · 3.36 Impact Factor