Estrogen serum concentration affects blood immune cell composition and polarization in human females under controlled ovarian stimulation

Estrogens modulate the immune system and possess anti-inflammatory properties. In line, immune cells express a variety of estrogen receptors (ER) including ER-alpha and -beta. In the present study, we examined the influence of 17beta-estradiol (E2) serum concentrations on blood leukocyte composition and their ex vivo polarization/activation status by FACS analysis in sub-fertile human females under controlled ovarian stimulation (COS). Using a set of cell-type and polarization-specific markers, we demonstrate that increased 17ß-estradiol (E2) serum concentrations yield an overall increase in leukocytes, neutrophils and monocytes but decreased lymphocytes. There was a clear ratio shift towards an increase in M2 monocytes with a protective quality and an increase in T-helper cells compared to a decrease in cytotoxic T-cells. These data support experimental findings and clinical trials, i.e. related to multiple sclerosis and other autoimmune-related diseases, that have shown a down-regulation of CD8(+) T cells and up-regulation of T-regulatory cells. Further studies have to pinpoint to which extent the immune system/-responsiveness of otherwise healthy female patients is affected by medium-term systemic E2 variations.