Regulation of dendritic cells by female sex steroids: Relevance to immunity and autoimmunity

Dendritic cells (DCs) are critical mediators of adaptive immunity, tolerance and autoimmunity. The human immune system exhibits sexual dimorphism, which is most evident in the female predominance of autoimmune diseases such as systemic lupus erythematosus (SLE). Female sex steroids are strongly implicated in mediating immune sexual dimorphism, in part because estrogen accentuates disease in several models of lupus autoimmunity. In contrast, progesterone may prevent disease development. While much investigation has focused on the effects of estrogen and progesterone on lymphocyte functions, far less attention has been paid to the effects of these hormones on DCs. Current evidence now indicates estrogen can activate DCs, while in contrast, progesterone inhibits DC functions. Thus, we hypothesize that the opposite effects these two hormones have on lupus autoimmunity reflect opposing effects on DC functions. Thus, through direct actions on DCs, female sex steroids may influence autoimmunity, immunity and tolerance.