Estrogen Receptor α Loss-of-Function Protects Female Mice From DSS-Induced Experimental Colitis

Males are at greater risk than females for developing ulcerative colitis (UC) and experiencing worse clinical disease1–3; the molecular basis for this sex bias remains unclear. An important regulatory mechanism of colonic homeostasis is via noncanonical estrogen receptor (ER) signaling. Very low levels of circulating estrogen are required to bind transmembrane and cytosolic ERs, such that immune responses in both sexes are subject to regulation by estrogen. Estrogen receptor β (ERβ) is expressed abundantly in the human colon,4,5 where it has a critical role in maintaining barrier function and colonic architecture.