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Mathilde Raverdeau Aurore Gely-Pernot Betty Féret Christine Dennefeld Gérard Benoit Irwin Davidson Pierre Chambon Manuel Mark Norbert B. Ghyselinck 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(41):16582-16587
Direct evidence for a role of endogenous retinoic acid (RA), the active metabolite of vitamin A in the initial differentiation and meiotic entry of spermatogonia, and thus in the initiation of spermatogenesis is still lacking. RA is synthesized by dedicated enzymes, the retinaldehyde dehydrogenases (RALDH), and binds to and activates nuclear RA receptors (RARA, RARB, and RARG) either within the RA-synthesizing cells or in the neighboring cells. In the present study, we have used a combination of somatic genetic ablations and pharmacological approaches in vivo to show that during the first, prepubertal, spermatogenic cycle (i) RALDH-dependent synthesis of RA by Sertoli cells (SC), the supporting cells of the germ cell (GC) lineage, is indispensable to initiate differentiation of A aligned into A1 spermatogonia; (ii) RARA in SC mediates the effects of RA, possibly through activating Mafb expression, a gene whose Drosophila homolog is mandatory to GC differentiation; (iii) RA synthesized by premeiotic spermatocytes cell autonomously induces meiotic initiation through controlling the RAR-dependent expression of Stra8. Furthermore, we show that RA of SC origin is no longer necessary for the subsequent spermatogenic cycles but essential to spermiation. Altogether, our data establish that the effects of RA in vivo on spermatogonia differentiation are indirect, via SC, but direct on meiotic initiation in spermatocytes, supporting thereby the notion that, contrary to the situation in the female, RA is necessary to induce meiosis in the male. 相似文献
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Intragenic deletion of the WDR45 gene in a male with encephalopathy,severe psychomotor disability,and epilepsy 下载免费PDF全文
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Umbilical cord blood plasma contains soluble NKG2D ligands that mediate loss of natural killer cell function and cytotoxicity 下载免费PDF全文
Steven T. Cox Raquel Laza‐Briviesca Hayley Pearson Bernat Soria Daniel Gibson Susana Gomez J. Alejandro Madrigal Aurore Saudemont 《European journal of immunology》2015,45(8):2324-2334
NK cells play a key role in innate elimination of virally infected or neoplastic cells but they can be circumvented by immunoevasive mechanisms enabling viral spread or tumor progression. Engagement of the NKG2D activating receptor with soluble forms of its ligand is one such mechanism of inducing NK cell hyporesponsiveness. Interestingly, this immunoevasive strategy among others is described at the maternal‐fetal interface where tolerance of the semi‐allogeneic fetus is required to allow successful human pregnancy. Understanding of maternal‐fetal tolerance is increasing but mechanisms preventing alloreactivity of fetal immune cells against the maternal host are less well understood. The study of umbilical cord blood has enabled insight of the fetal immune system, which appears immature and inert. We have found that soluble NKG2D ligands (sNKG2DLs) are present in cord blood plasma (CBP) and associate with adult NK cell hyporesponsiveness demonstrated by reduced CD107a expression and secretion of IFN‐γ upon stimulation. The capacity of NK cells to kill K562 cells or proliferate was also reduced by incubation with CBP; however, physical removal of sNKG2DL from CBP restored K562 lytic function and NKG2D expression. Therefore, our results strongly suggest sNKG2DLs are expressed in CBP as a mechanism of fetal‐maternal tolerance in human pregnancy. 相似文献
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Successful renal retransplantation after graft loss from BK polyomavirus infection in a human immunodeficiency virus‐positive patient 下载免费PDF全文
Aurore Barthélemy Nicolas Bouvier Renaud Verdon Valérie Chatelet Bruno Hurault de Ligny 《Transplant infectious disease》2016,18(6):946-949
We report the case of a human immunodeficiency virus‐seropositive patient whose initial kidney transplant failed because of BK polyomavirus‐induced nephropathy, and who underwent a second transplantation 3 years later. BK viruria was detected 1 day after transplantation. After 1 month, BK viremia developed along with a donor‐specific antibody. After decreasing tacrolimus and mycophenolic acid and 2 courses of intravenous immunoglobulins, BK viremia and donor‐specific antibody permanently disappeared, with stable renal function. 相似文献
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