Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat

Everts, Helen B.; Sundberg, John P.; Ong, David E.

doi:10.1016/j.yexcr.2005.04.026

Cited by 25 publications

(16 citation statements)

References 46 publications

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“…Airway epithelial cells express Aldh1a1 and might also constitute a source of GM-CSF. 31,35,36 In the skin, the RALDH2 and RALDH3 enzymes are highly expressed by hair follicles, 37,38 whereas GM-CSF is produced by keratinocytes and dermal fibroblasts. 39,40 Therefore, these recurrent features may explain the presence of ALDH ϩ DCs in the small intestine, lungs, and skin and point to the existence of cellular niches capable of inducing ALDH activity in DCs.…”

Section: Discussionmentioning

confidence: 99%

Skin-draining lymph nodes contain dermis-derived CD103− dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells

Guilliams

Crozat

Henri

et al. 2010

Blood

289

293

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Small intestinal CD103 ؉ dendritic cells (DCs) have the selective ability to promote de novo generation of regulatory T cells via the production of retinoic acid (RA). Considering that aldehyde dehydrogenase (ALDH) activity controls the production of RA, we used a flow cytometrybased assay to measure ALDH activity at the single-cell level and to perform a comprehensive analysis of the RA-producing DC populations present in lymphoid and nonlymphoid mouse tissues. RA-producing DCs were primarily of the tissue-derived, migratory DC subtype and can be readily found in the skin and in the lungs as well as in their corresponding draining lymph nodes. The RA-producing skin-derived DCs were capable of triggering the generation of regulatory T cells, a finding demonstrating that the presence of RA-producing, tolerogenic DCs is not restricted to the intestinal tract as previously thought. Unexpectedly, the production of RA by skin DCs was restricted to CD103 ؊ DCs, indicating that CD103 expression does not constitute a "universal" marker for RA-producing mouse DCs. Finally, Toll-like receptor (TLR) triggering or the presence of a commensal microflora was not essential for the induction of ALDH activity in the discrete ALDH ؉ DC subsets that characterize tissues constituting environmental interfaces. (Blood. 2010;115: 1958-1968 IntroductionThe vitamin A metabolite retinoic acid (RA) is a lipophilic molecule that controls the activity of a constellation of genes via binding to nuclear receptors. 1 Vitamin A is derived from the diet, and the liver constitutes a large reservoir of vitamin A in the form of retinyl esters. Retinyl esters are hydrolyzed to retinol and released into the blood. Once retinol enters cells expressing appropriate enzymes, it is converted successively into retinal and RA. The first step of the conversion is catalyzed by alcohol dehydrogenases and by microsomal retinol dehydrogenases that are expressed by most cells, including dendritic cells (DCs). The second step consists of the oxidation of retinal into RA and is catalyzed by 3 aldehyde dehydrogenases (ALDHs), known as RALDH1, 2, and 3 and encoded by the Aldh1a1, -2, and -3 genes, respectively. RALDH expression is limited to certain cell types and, despite the widespread availability of retinol, only cells expressing one of the RALDHs can oxidize retinaldehyde to RA.Conventional DCs (cDCs) and plasmacytoid DCs (pDCs) reside throughout their life cycle in secondary lymphoid organs and are denoted as lymphoid tissue-resident DCs to distinguish them from tissue-derived, migratory DCs (mDCs). 2 cDCs express intermediate levels of major histocompatibility complex (MHC) class II molecules and high levels of CD11c (MHCII inter CD11c high ), whereas mDCs express high levels of MHC class II molecules and intermediate to high levels of CD11c (MHCII high CD11c inter to high ). Recently, DCs that are located in gut-associated lymphoid tissue (GALT) and express Aldh1a2 have gained considerable attention because of their ability to produce RA. On migration to me...

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Section: Discussionmentioning

confidence: 99%

Skin-draining lymph nodes contain dermis-derived CD103− dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells

Guilliams

Crozat

Henri

et al. 2010

Blood

289

293

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“…They are expressed in many vitamin A sensitive cell types and are often coexpressed with CRBP-I. CRBP-I acts as a chaperone for retinol and retinal and directs them to these metabolizing enzymes (Everts et al, 2005) (Fig. 3).…”

Section: Oxidation Of All-trans Retinol To All-trans Retinalmentioning

confidence: 99%

Overview of retinoid metabolism and function

2006

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Retinoids (vitamin A) are crucial for most forms of life. In chordates, they have important roles in the developing nervous system and notochord and many other embryonic structures, as well as in maintenance of epithelial surfaces, immune competence, and reproduction. The ability of all-trans retinoic acid to regulate expression of several hundred genes through binding to nuclear transcription factors is believed to mediate most of these functions. The role of all-trans retinoic may extend beyond the regulation of gene transcription because a large number of noncoding RNAs also are regulated by retinoic acid. Additionally, extra-nuclear mechanisms of action of retinoids are also being identified. In organisms ranging from prokaryotes to humans, retinal is covalently linked to G protein-coupled transmembrane receptors called opsins. These receptors function as light-driven ion pumps, mediators of phototaxis, or photosensory pigments. In vertebrates phototransduction is initiated by a photochemical reaction where opsin-bound 11-cis-retinal is isomerized to all-trans-retinal. The photosensitive receptor is restored via the retinoid visual cycle. Multiple genes encoding components of this cycle have been identified and linked to many human retinal diseases. Central aspects of vitamin A absorption, enzymatic oxidation of all-trans retinol to all-trans retinal and all-trans retinoic acid, and esterification of all-trans retinol have been clarified. Furthermore, specific binding proteins are involved in several of these enzymatic processes as well as in delivery of all-trans retinoic acid to nuclear receptors. Thus, substantial progress has been made in our understanding of retinoid metabolism and function. This insight has improved our view of retinoids as critical molecules in vision, normal embryonic development, and in control of cellular growth, differentiation, and death throughout life.

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“…Also, CRBP1 and DHRS9 proteins express concurrently during estrus in the rat uterine lining (Rexer & Ong, 2002), and co-localize in multiple cells of the rat respiratory and urogenital tracts and pancreas, although there are mismatches, likely due to presence of RDH other than DHRS9 (Everts et al, 2005). The observation that CRBP1 co-localizes with either RALDH2 or 3 supports this conclusion.…”

Section: Diverse Metabolic Functions Of Cellular Retinol Binding-pmentioning

confidence: 99%

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

Napoli

2017

Pharmacology & Therapeutics

208

180

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Cellular binding-proteins (BP), including CRBP1, CRBP2, CRABP1, CRABP2, and FABP5, shepherd the poorly aqueous soluble retinoids during uptake, metabolism and function. Holo-BP promote efficient use of retinol, a scarce but essential nutrient throughout evolution, by sheltering it and its major metabolite all-trans-retinoic acid from adventitious interactions with the cellular milieu, and by imposing specificity of delivery to enzymes, nuclear receptors and other partners. Apo-BP reflect cellular retinoid status and modify activities of retinoid metabolon enzymes, or exert non-canonical actions. High ligand binding affinities and the nature of ligand sequestration necessitate external factors to prompt retinoid release from holo-BP. One or more of cross-linking, kinetics, and colocalization have identified these factors as RDH, RALDH, CYP26, LRAT, RAR and PPARβ/δ. Michaelis-Menten and other kinetic approaches verify that BP channel retinoids to select enzymes and receptors by protein-protein interactions. Function of the BP and enzymes that constitute the retinoid metabolon depends in part on retinoid exchanges unique to specific pairings. The complexity of these exchanges configure retinol metabolism to meet the diverse functions of all-trans-retinoic acid and its ability to foster contrary outcomes in different cell types, such as inducing apoptosis, differentiation or proliferation. Altered BP expression affects retinoid function, for example, by impairing pancreas development resulting in abnormal glucose and energy metabolism, promoting predisposition to breast cancer, and fostering more severe outcomes in prostate cancer, ovarian adenocarcinoma, and glioblastoma. Yet, the extent of BP interactions with retinoid metabolon enzymes and their impact on retinoid physiology remains incompletely understood.

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Immunolocalization of retinoic acid biosynthesis systems in selected sites in rat

Cited by 25 publications

References 46 publications

Skin-draining lymph nodes contain dermis-derived CD103− dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells

Skin-draining lymph nodes contain dermis-derived CD103− dendritic cells that constitutively produce retinoic acid and induce Foxp3+ regulatory T cells

Overview of retinoid metabolism and function

Cellular retinoid binding-proteins, CRBP, CRABP, FABP5: Effects on retinoid metabolism, function and related diseases

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