Although human twin studies have revealed the combined contribution of heritable and environmental factors in shaping immune system variability in blood, the contribution of these factors to immune system variability in tissues remains unexplored. The human uterus undergoes constant regeneration and is exposed to distinct environmental factors. To assess uterine immune system variation, we performed a system-level analysis of endometrial and peripheral blood immune cells in monozygotic twins. Although most immune cell phenotypes in peripheral blood showed high genetic heritability, more variation was found in endometrial immune cells, indicating a stronger influence by environmental factors. Cytomegalovirus infection was identified to influence peripheral blood immune cell variability but had limited effect on endometrial immune cells. Instead, hormonal contraception shaped the local endometrial milieu and immune cell composition with minor influence on the systemic immune system. These results highlight that the magnitude of human immune system variation and factors influencing it can be tissue specific.

中文翻译：

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组织特异性非遗传性影响驱动子宫内膜免疫系统变异


尽管人类双胞胎研究揭示了遗传因素和环境因素在塑造血液中免疫系统变异性方面的共同作用，但这些因素对组织中免疫系统变异性的影响仍有待探索。人类子宫经历不断的再生并暴露于不同的环境因素。为了评估子宫免疫系统的变异，我们对同卵双胞胎的子宫内膜和外周血免疫细胞进行了系统级分析。尽管外周血中大多数免疫细胞表型表现出较高的遗传性，但子宫内膜免疫细胞的变异较多，表明受环境因素的影响更强。巨细胞病毒感染被确定会影响外周血免疫细胞的变异性，但对子宫内膜免疫细胞的影响有限。相反，激素避孕塑造了局部子宫内膜环境和免疫细胞组成，对全身免疫系统影响较小。这些结果强调，人类免疫系统变异的程度和影响它的因素可能是组织特异性的。