title: Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development.
abstract: Vitamin A deficiency is known to be accompanied with immune deficiency and susceptibility to a wide range of infectious diseases. Experimental evidence suggests that the active metabolites of vitamin A that mediate its effects on the immune system are the retinoic acids (RA), which are ligands for the nuclear RA receptor (RAR) family. RA were previously shown both to promote proliferation and to regulate apoptosis of thymocytes. In this study we detected the age-dependent mRNA expression of retinaldehyde dehydrogenases (RALDH1 and 2), cellular RA binding protein-II and CYP26A, proteins responsible for the synthesis, nuclear transport and degradation of RA in the postnatally developing thymus. RALDH1 was located in thymic epithelial cells. However, the amount of all-trans RA in thymic homogenates was close to the detection limit, suggesting that in this tissue all-trans RA is not the main RAR-regulating product of retinol metabolism. At the same time, by measuring the induction of a RAR-responsive transgene in two independent transgenic mouse strains, we demonstrated the production of an RAR-activating ligand, which was age and RALDH dependent. Our data provide evidence for the existence of endogenous retinoid synthesis in the thymus and suggest that retinoids similar to glucocorticoids might indeed be involved in the regulation of thymic proliferation and selection processes by being present in the thymus in functionally effective amounts.
authors: Department of Biochemistry and Molecular Biology, Signaling and Apoptosis Research Group, Hungarian Academy of Sciences, Research Center of Molecular Medicine, University of Debrecen, Debrecen, Hungary.
authors: Ildikó
authors: I
authors: Kiss
authors: Ralph
authors: R
authors: Rühl
authors: Eva
authors: E
authors: Szegezdi
authors: Britta
authors: B
authors: Fritzsche
authors: Beáta
authors: B
authors: Tóth
authors: Judit
authors: J
authors: Pongrácz
authors: Thomas
authors: T
authors: Perlmann
authors: László
authors: L
authors: Fésüs
authors: Zsuzsa
authors: Z
authors: Szondy
mesh_terms: D000445:Aldehyde Oxidoreductases / Q000276:immunology / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000276:immunology; D003577:Cytochrome P-450 Enzyme System / Q000276:immunology / Q000378:metabolism; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D018168:Receptors, Retinoic Acid / Q000276:immunology / Q000378:metabolism*; D000072516:Retinoic Acid 4-Hydroxylase; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000254:growth & development* / Q000276:immunology* / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D008024:Ligands; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; C082927:retinoic acid binding protein I, cellular; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase; D000445:Aldehyde Oxidoreductases; C470579:RALDH2 protein, mouse