Our Environment Shapes Us: The Importance of Environment and Sex Differences in Regulation of Autoantibody Production.
Our Environment Shapes Us: The Importance of Environment and Sex Differences in Regulation of Autoantibody Production.
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DOI：
10.3389/fimmu.2018.00478
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发表时间：
2018
影响因子：
7.3
通讯作者：
Ahmed SA
中科院分区：
文献类型：
--
作者：
Edwards M;Dai R;Ahmed SA
因此，男性和女性免疫系统对病原体、环境侮辱或自身抗原的反应能力以及随后对免疫调节的影响之间存在差异。一般来说，与男性相比，女性对致病刺激和疫苗的反应更强烈，抗体、促炎细胞因子和趋化因子的产生增加。虽然对不同刺激的免疫反应的性别差异的确切原因尚不清楚，但女性对传染病的抵抗力更强，更有可能患上自身免疫性疾病。与生俱来的(即性激素、性染色体等)而外在因素(微生物群组成、外部触发因素和免疫调节剂)似乎影响性别间免疫反应的总体结果。有证据表明，环境污染物[如内分泌干扰物(EDCs)]与宿主白细胞之间的相互作用影响免疫系统对外源性和内源性侮辱做出反应的能力，和/或在威胁消除后恢复正常活动的能力。从本质上讲，男性和女性对外部触发因素有不同的免疫反应。在这篇综述中，我们描述了包括内皮细胞在内的环境化学物质如何通过表观遗传状态的改变(如调节microRNA表达、基因甲基化或组蛋白修饰状态)、直接和间接激活雌激素受体来驱动激素效应，以及对微生物感知和宿主微生物区系组成的差异调控，从而对免疫反应的结果产生性别差异影响。综上所述，一个有趣的问题出现了，即个人的环境如何直接和间接地促进免疫反应的改变，自身抗体产生的失调，并影响自身免疫性疾病的发展。很少有研究利用控制良好的男女队列来探索EDC暴露的性别差异及其对自身免疫性疾病发展的影响。在自身免疫性疾病的动物模型中结合多种环境因素的转译研究对于确定潜在的致病因素之间的相互关系是必要的。自身抗体的存在与否并不是疾病的可靠预测指标。因此，未来的研究应该结合所有的易感性/影响因素，结合个体基因组学、表观基因组学和蛋白质组学，以开发一种以个性化药物方式更好地预测、诊断和治疗自身免疫性疾病的模型。
Consequential differences exist between the male and female immune systems’ ability to respond to pathogens, environmental insults or self-antigens, and subsequent effects on immunoregulation. In general, females when compared with their male counterparts, respond to pathogenic stimuli and vaccines more robustly, with heightened production of antibodies, pro-inflammatory cytokines, and chemokines. While the precise reasons for sex differences in immune response to different stimuli are not yet well understood, females are more resistant to infectious diseases and much more likely to develop autoimmune diseases. Intrinsic (i.e., sex hormones, sex chromosomes, etc.) and extrinsic (microbiome composition, external triggers, and immune modulators) factors appear to impact the overall outcome of immune responses between sexes. Evidence suggests that interactions between environmental contaminants [e.g., endocrine disrupting chemicals (EDCs)] and host leukocytes affect the ability of the immune system to mount a response to exogenous and endogenous insults, and/or return to normal activity following clearance of the threat. Inherently, males and females have differential immune response to external triggers. In this review, we describe how environmental chemicals, including EDCs, may have sex differential influence on the outcome of immune responses through alterations in epigenetic status (such as modulation of microRNA expression, gene methylation, or histone modification status), direct and indirect activation of the estrogen receptors to drive hormonal effects, and differential modulation of microbial sensing and composition of host microbiota. Taken together, an intriguing question develops as to how an individual’s environment directly and indirectly contributes to an altered immune response, dysregulation of autoantibody production, and influence autoimmune disease development. Few studies exist utilizing well-controlled cohorts of both sexes to explore the sex differences in response to EDC exposure and the effects on autoimmune disease development. Translational studies incorporating multiple environmental factors in animal models of autoimmune disease are necessary to determine the interrelationships that occur between potential etiopathological factors. The presence or absence of autoantibodies is not a reliable predictor of disease. Therefore, future studies should incorporate all the susceptibility/influencing factors, coupled with individual genomics, epigenomics, and proteomics, to develop a model that better predicts, diagnoses, and treats autoimmune diseases in a personalized-medicine fashion.