The size, cellularity and lymphocyte subpopulations of STRA6 KO thymus and spleen were comparable to those of their wild type (WT) controls. T cells in an analogous manner as their WT counterparts.In vivoexperiments revealed that anti-viral immune responses to lymphocytic Proparacaine HCl choriomeningitis virus in KO mice were comparable to those of WT controls. We also demonstrated that STRA6 KO and WT mice had similar glucose tolerance. Total vitamin A levels are dramatically lower in the eyes of KO mice as compared to those of WT mice, but the levels in other organs were not significantly affected after STRA6 deletion under vitamin A sufficient conditions, indicating that the eye is the mouse organ most sensitive to the loss of STRA6. Our results demonstrate that 1) in vitamin A sufficiency, the deletion of STRA6 in T Proparacaine HCl cells does no affect the T-cell immune responses so-far tested, including those depend on STAT5 signaling; 2) STRA6-independent vitamin A uptake compensated the lack of STRA6 in lymphoid organs under vitamin A sufficient conditions in mice; 3) STRA6 is critical for vitamin A uptake in the eyes even in vitamin A sufficiency. == Introduction == During T-cell immune responses, naive T cells are activated by stimuli through TCR in the company of co-stimulation signals, Proparacaine HCl and undergo multiple rounds of proliferation before entering the differentiation phase, after which they become effector T cells. The expression of many molecules is modulated during activation and differentiation stages, with some of them playing pivotal regulatory roles, while others exert support and house-keeping functions to cope with increased metabolic demands. We undertook unbiased exploration with DNA microarray analysis of molecules up- or down-regulated in T cells within the first 16 h after stimulation by anti-CD3 with a view to identifying those that are critical in the early T-cell activation stage. A group of molecules with Igf1r the highest levels of altered expression in activated T cells was chosen, with resting T cells as reference, and verified by Northern blotting analysis. STRA6 (stimulated by retinoic acid gene 6) is among those that have been validated. We generated STRA6 gene knockout (KO) mice to assess the significance of its up-regulation in T-cell activation and, consequently, T-cell immune responses. At the outset of our investigation in 2004, no function was ascribed to STRA6, a 74-kDa protein with multiple transmembrane domains that was first identified in retinoic acid-stimulated P19 embryonic carcinoma cells upon retinoic acid stimulation[1]. In 2007, Kawaguchi et al. used an unbiased Proparacaine HCl technique to Proparacaine HCl identify STRA6 as a specific cell-surface receptor for plasma retinol binding protein (RBP) and showed that STRA6 mediates cellular vitamin A uptake from holo-RBP (RBP/vitamin A complex) in bovine retinal pigment epithelium cells[2]. STRA6-mediated vitamin A uptake from holo-RBP is coupled to intracellular proteins as confirmed by several independent studies[1][5], and its mechanism in coupling to specific intracellular proteins has been elucidated[4]. Pasutto et al.[6]observed that mutations in STRA6 correlated with many eye, heart, diaphragm and lung malformations as well as mental retardation in Matthew-Wood syndrome in humans, corroborating its reported roles in vitamin A uptake by cells as vitamin A is vital in organogenesis. Recent reports indicate that single nucleotide polymorphisms or mutations in STRA6 gene are correlated with the congenital eye malformations microphthalmia, anophthalmia and coloboma[7],[8]as well as Matthew-Wood syndrome[9]. Genetic null mutation of STRA6 in mice results in significant retinoid reduction in the retinal pigment epithelium and neurosensory retina, diminished visual responses and eye morphology, although the last-mentioned defect is not as serious as in patients with STRA6 mutations[10]. There is a report suggesting that STRA6 is not only a vitamin A transporter but can also function as a cytokine receptor. Upon binding with holo-RBP, STRA6 is phosphorylated at tyrosine residue 643, which, in turn, recruits and triggers JAK2 and STAT5 activation[11]. The ascribed roles of STRA6 in vitamin A transport and the STAT5 signalling pathway are certainly relevant to T-cell activation and function. Retinoids are known to modulate Th1 (T helper 1), Th2, Th17 and reglulatory T (Treg) cell development and function[12][17]. At the molecular level, it has been demonstrated that retinoic acid opens up the FoxP3 promoter tertiary structure for activated FoxP3 transcription[18]. RAR can interact with STAT5a and b[19], which are critical molecules in the signaling pathway of a key T activation.