17β-estradiol promotes myeloid-derived suppressor cells functions and alleviates inflammatory bowel disease by activation of Stat3 and NF-κB signalings.

Inflammatory bowel disease (IBD) describes a group of clinically common autoimmune diseases characterized by chronic intestinal inflammation, with gender differences in prevalence. Estrogen has been previously shown to exert anti-inflammatory action in IBD development, however, the mechanisms remain obscure. Recent research has revealed that myeloid-derived suppressor cells (MDSCs) play a protective role in IBD pathogenesis.

Mutation of aspartic acid 262 on estrogen receptor abrogates estradiol signaling pathway.

Objective: ERα (estrogen receptor alpha) exerts nuclear genomic actions and membrane-initiated non-genomic effects. The mutation of aspartic acid into alanine revealed the critical role of aspartic acid 258 (corresponding to mouse amino acid site 262) of ERα for non-nuclear function. Our previous study revealed that this mutation blocked estrogen's non-genomic effects on vascular endothelial HS release.