Most studies about RA are focused on its function in embryo development. group. The expression of RORt 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 RAR protein levels in peri-implantation uterus after gene vaccine immunization and researches using the specific agonist and antagonist against RAR suggested that RAR 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 GSK163090 RAR in mouse peri-implantation. Keywords:cyp26a1, Th17, pregnancy, RORt, RA, RAR == Introduction == As a metabolic enzyme of the vitamin A metabolite retinoic acid (RA), cytochrome P450 26a1 (cyp26a1) is a member of the cyp26a family [12]. The cytochrome P450 (CYP) family is a superfamily of haem-binding monooxygenases that catalyses numerous important biological reactions, like non-specific oxidative conversions of many steroids, lipids, and a variety of xenobiotics and environmental toxins [2]. This superfamily is so large that contains at least 74 families and each family is constituted by a plurality of family members. These family members are distinct from their particular distribution, biologically active pattern or preferred substrates. Cyp26a1 is expressed in the female reproductive tract [4,5] and takes all-trans-RA (at-RA) as its preferred substrate. Our previous work shown that the significant up-regulation of cyp26a1 in the endometrial epithelial cells of mice on D5 and D6 of gestation [6], the key time for embryo implantation, suggested its important role in peri-implantation. Other studies also showed that the expression of cyp26a1 in GSK163090 endometrial epithelial cells is regulated through progesterone, but is not significantly influenced through the co-administration of oestrogen [5]. Interference to cyp26a1 could resulting in serious consequences of pregnancy; the implantation sites number was significantly reduced after the intrauterine injection of cyp26a1-specific antisense oligos or anti-cyp26a1 antibody Itga10 on D3 of pregnancy [6]. Accordingly, the expression of cellular retinoic acidbinding protein 1 and tissue trans glutaminase was markedly increased in the uterine luminal epithelium after the intrauterine injection [6]. These researches prompted that the cyp26a1 role in successful pregnancy can never be overlooked, whereas the specific mechanism involving cyp26a1 and foetal loss remains unclear. Retinoic acid (RA) is the substrate of cyp26a and also a largely used medicine in clinic. It has multiple isomers like 13-cis-RA, 9-cis-RA and at-RA. Among them, at-RA is the preferred substrate of cyp26a1 and the potential inducer of cyp26a1 expression in the liver [1,2,7,8]. As the active metabolite of vitamin A, RA is a crucial factor for embryonic development [9], meiotic initiation [10] and the regulation of immunity [11]. Recent studies have shown that RA is also essential for the development of certain immune cell subtype. Mucidaet al. identified the vitamin A metabolite retinoic acid as a key regulator of TGF-dependent immune responses, which inhibits the IL-6driven induction GSK163090 of pro-inflammatory Th17 cells [12]. It is already known that mammalian immune system is remodelled during peri-implantation to tolerate paternal alloantigens and GSK163090 simultaneously protect the female parent from infections for successful pregnancy. T-helper (Th) cells play a central GSK163090 role in this process [13,14]. On the basis of this information, we speculated that Th17 cells may involved in the role of cyp26a1 during peri-implantation. However, the certainty of this and mechanism underlying needs further research. The aim of this study was to identify the precise target immune cell subset of cyp26a1 in peri-implantation and explore if the role of cyp26a1 depends on RA. Here, we used a cyp26a1 gene immunization model, which has been proven to make enormous impacts on mouse pregnancy to explore the target cell group.