Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development

TY - JOUR

T1 - Retinoid receptor-activating ligands are produced within the mouse thymus during postnatal development

AU - Kiss, Ildikó

AU - Rühl, Ralph

AU - Szegezdi, Eva

AU - Fritzsche, Britta

AU - Tóth, Beáta

AU - Pongrácz, Judit

AU - Perlmann, Thomas

AU - Fésüs, László

AU - Szondy, Zsuzsa

PY - 2008/1

Y1 - 2008/1

N2 - 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.

AB - 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.

KW - Aldehyde Oxidoreductases

KW - Animals

KW - Apoptosis

KW - Cytochrome P-450 Enzyme System

KW - In Situ Hybridization

KW - In Situ Nick-End Labeling

KW - Ligands

KW - Mice

KW - Mice, Transgenic

KW - Polymerase Chain Reaction

KW - RNA, Messenger

KW - Receptors, Retinoic Acid

KW - Retinoic Acid 4-Hydroxylase

KW - T-Lymphocytes

KW - Thymus Gland

KW - Tretinoin

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1002/eji.200737342

DO - 10.1002/eji.200737342

M3 - SCORING: Journal article

C2 - 18085670

VL - 38

SP - 147

EP - 155

JO - EUR J IMMUNOL

JF - EUR J IMMUNOL

SN - 0014-2980

IS - 1

ER -