17β-estradiol contributes to the accumulation of myeloid-derived suppressor cells in blood by promoting TNF-α secretion

Abstract Estrogens are strongly implicated in gender differences in immune responses by influencing the development and activation of immune cells. Recent studies have shown that myeloid-derived suppressor cells (MDSCs), derived from CD11b(+)Gr-1(+) myeloid cells under pathological conditions, play vital roles in modulating immune responses. However, it is still unknown the effects of estrogens on MDSCs. In the present study, we investigated the effects and mechanisms of estrogens on regulating the accumulation of MDSCs. It was found that, compared with male patients with systemic lupus erythematosus (SLE), female patients with SLE showed a higher frequency of MDSCs in peripheral blood mononuclear cells and a higher level of tumor necrosis factor α (TNF-α) in serum. Notably, estradiol level in the serum of female patients with SLE was positively correlated with the frequency of MDSCs. Moreover, 17β-estradiol could promote TNF-α-induced accumulation of MDSCs in vivo by increasing the fundamental frequency of CD11b(+)Gr-1(+) cells. Furthermore, 17β-estradiol promoted the secretion of TNF-α in vivo, which contributed to the increase of the frequency of CD11b(+)Gr-1(+) cells. In addition, it was also found that female mice showed a higher frequency of CD11b(+)Gr-1(+) cells and a higher TNF-α level in blood than the age-matched male mice. These data indicate that 17β-estradiol contributes to the accumulation of MDSCs in blood by promoting TNF-α secretion, which increases the fundamental frequency of CD11b(+)Gr-1(+) cells. Our findings provide a new insight into the mechanism of gender difference in the prevalence of inflammation and autoimmune diseases.