Center for Gender Specific Medicine, Istituto Superiore di Sanità, Rome, Italy.
Biol Sex Differ. 2021 Jan 12;12(1):12. doi: 10.1186/s13293-021-00358-3.
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.
在过去的几十年中，维生素 D 在免疫调节中的核心作用已得到充分证实。维生素 D 的活性形式，即 1,25-二羟维生素 D，通过与维生素 D 受体相互作用，对先天和适应性免疫系统发挥不同的作用，其中包括抑制炎症和促进耐受反应。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，这些疾病在女性和男性之间通常存在显著差异。值得注意的是，最近的许多研究表明维生素 D 和性激素雌激素之间存在交叉对话。雌激素对免疫反应的影响可能有利于 Th1 表型或 Th2 表型，具体取决于激素浓度。因此，雌激素介导的自身免疫作用似乎因其浓度而异，但也取决于不同自身免疫性疾病（即 Th1 或 Th2 介导的疾病）的发病机制。值得注意的是，已经证明雌激素可以增强维生素 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产生更强的抗炎反应。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，芳香酶将睾丸激素转化为雌激素，从而导致雌激素水平降低。总的来说，现有数据使我们能够假设基于维生素 D 的治疗方法在女性中的保护作用更高，至少在生育年龄比男性更高。需要进一步的研究来扩大目前对维生素 D 在性别和性别视角下的免疫调节作用的认识，为自身免疫性疾病的个体化治疗方法铺平道路。
