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.

Myeloid-derived suppressor cells contribute to systemic lupus erythaematosus by regulating differentiation of Th17 cells and Tregs

“…However, all these studies are still limited to animal experiments. • Strikingly, in our previous study, proportions of MDSCs were expanded in SLE patients [6], which was in contrast with other studies by reporting a reduction in MDSC numbers in lupusprone (NZB×NZW)F1 mice. As is well known, MDSCs can be further divided into M-MDSCs and G-MDSCs.…”

“…However, these studies draw a different conclusion on the proportions of MDSCs in SLE [3][4][5]. Strikingly, in our previous study, the proportion of MDSCs was expanded in SLE patients [6], which was in contrast with other studies that found a reduction in MDSC numbers in lupus-prone (NZB×NZW)F1 mice. In addition, previous study failed to explore the mechanism of function changes in MDSCs in SLE [3][4][5].…”

Altered crosstalk of estradiol and progesterone with Myeloid‐derived suppressor cells and Th1/Th2 cytokines in early miscarriage is associated with early breakdown of maternal‐fetal tolerance

“…9,10 However, E2 and MDSCs mutualistic functional relationship during pregnancy and in pathological setting like early miscarriage is still unexplored story and present work is a forward step to understand the same. Recent reports in cancer patients have shown that 17β-estradiol (E2) promotes accumulation of MDSCs in blood through the secretion of TNF-α.…”

“…Recent reports in cancer patients have shown that 17β-estradiol (E2) promotes accumulation of MDSCs in blood through the secretion of TNF-α. 9,10 However, E2 and MDSCs mutualistic functional relationship during pregnancy and in pathological setting like early miscarriage is still unexplored story and present work is a forward step to understand the same. E2 and P4 is also a potent regulator of Th1/Th2 cytokines balance and help in the production of Th2/anti-inflammatory cytokines which are helpful in building a conducive systemic milieu for healthy pregnancy.…”

LF-MF suppresses the colon cancer via regulating the function of MDSCs

“…+ GR-1 + ) [28] . 目前认 为, MDSCs发挥免疫抑制功能主要依赖于精氨酸酶 (ARG-1) [29] , 一氧化氮合酶(iNOS) [28] , ROS [30,31] , IL-1β [32] , IDO [33] 等因子的产生. 10 0 10 0 10 1 10 2 10 3 10 4 Q1 10 0 10 0 10 1 10 2 10 3 10 4 Q1 3.50% [34] .…”