Estrogen's contribution to autoimmune inflammation

Autoimmunity is now ubiquitous in both genders but it has long been known that female gender dominance is associated with an estrogen effect. A research article published in Science Signaling demonstrates that autoimmune inflammation occurs through stimulation of estrogen receptor alpha (ERα). The authors note about gender and autoimmunity:

"It has long been appreciated that most autoimmune disorders are characterized by increased prevalence in females, suggesting a potential role for sex hormones in the etiology of autoimmunity."

They studied how estrogen receptor α (ERα) contributes to autoimmune diseases by examining the effect of deleting ERα in the T lymphocytes of their study animals.

'Turning off' estrogen receptor alpha reduces autoimmunity

By deleting the receptor they were able to wind down autoimmune T cell activity and increase a critical factor for tolerance.

"We found that ERα deletion in T cells reduced their pathogenic potential in a mouse model of colitis and correlated with transcriptomic changes that affected T cell activation. ERα deletion in T cells contributed to multiple aspects of T cell function, including reducing T cell activation and proliferation..."

Additionally, regulatory T cell activity that dampens excessive inflammation was increased as ERα deletion also acted by...

"...increasing the expression of Foxp3, which encodes a critical transcription factor for the differentiation and function of regulatory T cells."

An accompanying editorial comment summarizes their findings:

"Mohammad et al. identify a direct role for the female sex hormone estrogen in the development of autoimmune T cell responses. Deletion of estrogen receptor α (ERα) in T cells reduced disease burden in a mouse model of colitis. ERα-expressing T cells were more activated after stimulation, proliferated more, and expressed more proinflammatory cytokines than T cells lacking this receptor. Conversely, ERα-deficient T cells were more readily skewed to a regulatory T cell phenotype. Together, these data identify a role for direct sex hormone–dependent activation of T cells in autoimmune responses."

Men are also affected by estrogen excess

Clinicians should bear in mind that constant exposure to estrogen-mimicking chemicals in the environment and conversion of testosterone by aromatase activity in visceral fat (accumulated due to insulin resistance), men are also subject to ERα overstimulation.It should go without saying that hormone replacement therapy in both genders should administered and responses over time tracked with maximum diligence. The authors conclude:

"Thus, these data demonstrate that ERα in T cells plays an important role in inflammation and suggest that ERα-targeted immunotherapies could be used to treat autoimmune disorders."

Readers may also be interested in Breast cancer, autoantibodies and autoimmune inflammation.