title: Regulation of cyp26a1 on Th17 cells in mouse peri-implantation.
abstract: Cytochrome P450 26A1 (cyp26a1) is expressed in the mouse uterus during peri-implantation. The repression of this protein is closely associated with a reduction in implantation sites, suggesting a specific role for cyp26a1 in pregnancy and prompting questions concerning how a metabolic enzyme can generate this distinct outcome. To explore the effective downstream targets of cyp26a1 and confirm if its role in peri-implantation depends on its metabolic substrate RA (retinoic acid), we characterized the changes in the peripheral blood, spleen and uterine implantation sites using the cyp26a1 gene vaccine constructed before. Flow cytometry results showed a significant increase in CD4(+) RORγt(+) Th17 cells in both the peripheral blood and spleen in the experimental group. The expression of RORγt and IL-17 presented the Th17 cells reduction in uterus followed by the suppression of cyp26a1 expression. For greater certainty, cyp26a1 antibody blocking model and RNA interference model were constructed to determine the precise target immune cell group. High performance liquid chromatography results showed a significant increase in uterine at-RA followed by the immunization of cyp26a1 gene vaccine. Both the ascertain by measuring RARα protein levels in peri-implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RARα suggested that RARα may be the main RA receptor for signal transduction. These results provided more evidence for the signal messenger role of RA in cyp26a1 regulation from the other side. Here, we showed that the cyp26a1-regulated Th17 cells are dependent on at-RA signalling, which is delivered through RARα in mouse peri-implantation.
authors: State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
authors: Hai-Yan
authors: HY
authors: Liu
authors: Huhe
authors: H
authors: Chao
authors: Zhen-Kun
authors: ZK
authors: Liu
authors: Hong-Fei
authors: HF
authors: Xia
authors: Zhihui
authors: Z
authors: Song
authors: Ying
authors: Y
authors: Yang
authors: Jing-Pian
authors: JP
authors: Peng
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D007114:Immunization; D016086:Lentivirus / Q000378:metabolism; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D010957:Plasmids / Q000378:metabolism; D011247:Pregnancy; D051381:Rats; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011995:Recombination, Genetic / Q000235:genetics; D000072516:Retinoic Acid 4-Hydroxylase; D000072482:Retinoic Acid Receptor alpha; D013154:Spleen / Q000187:drug effects / Q000378:metabolism; D058504:Th17 Cells / Q000187:drug effects / Q000201:enzymology*; D014212:Tretinoin / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; C000607072:Rara protein, mouse; C000607073:Rara protein, rat; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; C000607080:Cyp26a1 protein, mouse; D000072516:Retinoic Acid 4-Hydroxylase
keywords: RA; RARα; RORγt; Th17; cyp26a1; pregnancy