Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion.
Recipient sex and estradiol levels affect transplant outcomes in an age-specific fashion.
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DOI：
10.1111/ajt.16611
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发表时间：
2021-10
期刊：
影响因子：
--
通讯作者：
Tullius SG
中科院分区：
文献类型：
--
作者：
Maenosono R;Nian Y;Iske J;Liu Y;Minami K;Rommel T;Martin F;Abdi R;Azuma H;Rosner BA;Zhou H;Milford E;Elkhal A;Tullius SG
性别特异性的影响已被证明对各种疾病。供体或受体的性别和性激素水平是否影响同种免疫反应仍不清楚。在对超过400.000例SRTR列出的肾移植患者进行的单因素和多因素分析中，我们发现年轻女性受者的死亡删失移植物存活率较低，与供体性别无关。与此相反，移植物的存活率是上级在老年女性受体，这表明受体性激素的染色体性别不匹配的影响。这些临床变化在实验性皮肤和心脏移植模型中进行了描述，显示卵巢切除的年轻女性受者的移植物存活时间延长。相比之下，卵巢切除和初治老年女性受者的移植物存活率相当。年轻的卵巢切除小鼠表现出数量减少和受损的T细胞增殖。雌性激素的降低抑制了CD 4 + T细胞产生IFN-γ和IL-17+，同时增加了全身T细胞计数。体外雌二醇浓度的增加促进了幼稚CD 4 + T细胞向Th 1细胞的转变;高生理雌二醇浓度抑制了Th 1应答，促进了T细胞增殖，延长了移植物存活。因此，临床观察表明，年龄特异性移植物存活模式在女性受体。雌激素水平，反过来，影响T细胞亚群的命运，提供有关年龄和性别特异性同种异体免疫的相关和新的信息。
Sex-specific influences have been shown for a variety of diseases. Whether donor or recipient sex and sex-hormone levels impact alloimmune responses remains unclear. In uni- and multifactorial analyses of more than 400.000 SRTR listed kidney transplant patients, we found that younger female recipients had an inferior death-censored graft survival that was independent of donor sex. In contrast, graft survival was superior in older female recipients, suggesting the impact of recipient sex-hormones over chromosomal sex mismatches. Those clinical changes were delineated in experimental skin and heart transplant models showing a prolongation of graft survival in ovariectomized young female recipients. In contrast, graft survival was comparable in ovariectomized and naïve old female recipients. Young ovariectomized mice showed reduced amounts and a compromised T cell proliferation. Deprivation of female hormones dampened the production of IFN-γ and IL-17+ by CD4+ T cells while augmenting systemic counts of T regs. Increasing estradiol concentrations in-vitro promoted the switch of naïve CD4+ T-cells into Th1 cells; high physiological estradiol concentrations dampening Th1 responses, promoted T regs, and prolonged graft survival. Thus, clinical observations demonstrate age-specific graft survival patterns in female recipients. Estrogen levels, in turn, impact the fate of T-cell subsets, providing relevant and novel information on age and sex-specific alloimmunity.
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DOI：
10.1016/j.jsbmb.2015.09.039
发表时间：
2016-06
期刊：
The Journal of steroid biochemistry and molecular biology
影响因子：
--
作者：
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通讯作者：
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DOI：
10.1111/ajt.16218
发表时间：
2021-03
期刊：
American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
影响因子：
--
作者：
Heinbokel T;Quante M;Iske J;Nian Y;Maenosono R;Minami K;Liu Y;Azuma H;Elkhal A;Tullius SG
通讯作者：
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影响因子：
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