Over the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

中文翻译：

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维生素 D 在自身免疫性疾病中的作用：性别会有所作为吗？

在过去的几十年里，维生素 D 在免疫调节中的核心作用已经得到很好地确立。维生素 D 的活性形式，即 1,25-二羟基维生素 D，通过与维生素 D 受体的相互作用，对先天性和适应性免疫系统发挥不同的活性，其中包括抑制炎症和促进耐受性反应。维生素 D 不足与自身免疫性疾病有关，由于遗传、表观遗传、激素和环境因素，女性和男性之间通常表现出显着差异。值得注意的是，最近的一些研究表明维生素 D 和性激素雌激素之间存在相互影响。雌激素介导的对免疫反应的影响可能有利于 Th1 谱或 Th2 谱，这取决于激素浓度。因此，雌激素介导的效应似乎对自身免疫的影响取决于其浓度以及不同自身免疫疾病（即 Th1 或 Th2 介导的疾病）的致病机制。值得注意的是，雌激素已被证明可以增强维生素 D 的功能，有利于其积累，并增加维生素 D 受体的表达，从而导致女性比男性更有效的抗炎反应。另一方面，维生素 D 已被证明可以下调免疫细胞中芳香酶的表达，芳香酶将睾酮转化为雌激素，导致雌激素水平下降。总体而言，现有数据使我们可以假设基于维生素 D 的治疗方法对女性（至少在育龄期）的保护作用高于男性。