Vitamin D : Autoimmunity and Gender

Background: Vitamin D deficiency is considered a risk factor for autoimmune diseases. Vitamin D and its analogues have been proposed as therapeutic tools in autoimmunity considering their exquisite immunoregulatory effect against over-reactivity towards tolerance. Autoimmune diseases, nowadays recognized as emerging non communicable diseases, are characterized by a significant female bias. This sexual dimorphism seems related to sex hormones, which differently affect male and female immune systems. Males show higher immunosuppression, maybe due to androgens; the greater female immunoreactivity and competence, likely related to estrogens, lead to a greater resilience to infections but also to a higher risk for autoimmunity. Higher interest could be given to vitamin D-based supplementation or therapy for autoimmune diseases in relation to gender as well. Objective: This review aims to discuss the role of vitamin D in autoimmune diseases with a view inside gender-related differences, in light of the interplay between vitamin D and sex hormones, especially estrogens. Results: Some beneficial effects against autoimmune processes seem to be allowed by vitamin D acting in synergy with estrogens. This observation suggests that possible differences of vitamin D effects depend on the context in which this hormone is active. Conclusion: Rather sex-related differences of “absolute” vitamin D levels, the role of gender- dependent factors affecting vitamin D action seems to be critical. Gender and sexual hormones could be included as variables when evaluating the potential power of vitamin D receptor agonists as novel pharmacological tools to approach autoimmune diseases.