Estrogen-mediated immunosuppression in autoimmune diseases

Abstract

Gender affects the susceptibility to many autoimmune diseases. Women have an increased risk of developing diseases such as rheumatoid arthritis and multiple sclerosis compared with men. The female preponderance is believed to depend in part on the influence of sex hormones on the immune system. The mechanism of estrogen-induced immune suppression both in human autoimmune diseases and their experimental animal model counterparts is discussed. In addition, the mechanisms of estrogen and anti-estrogens are discussed in relation to their possible use as future therapeutic anti-inflammatory agents.

Estrogen anti-inflammatory activity in brain: A therapeutic opportunity for menopause and neurodegenerative diseases

“…This sexual dimorphism may be due to multiple factors; certainly gender-related differences in immune responsiveness are part of the cause, but sex hormones are likely to play a significant role ( [64,110]) as indicated by a series of observations: (a) the first clinical symptoms of MS develop post-puberty; (b) increased levels of sex hormones produced during pregnancy are associated with a significant reduction in the severity of MS; (c) MS clinical symptoms are often exacerbated postpartum, a time characterized by significant alternations in sex hormone levels; (d) MS symptoms are altered also during the menstrual cycle ( [1,16,45,127,188]). …”

T Lymphocytes Do Not Directly Mediate the Protective Effect of Estrogen on Experimental Autoimmune Encephalomyelitis

“…[1][2][3] Gender bias in autoimmune disease and other evidence suggests that sex steroid hormones play a role in regulating immune responses. 4,5 Immunomodulatory actions of estrogen appear to result from effects on immune cytokine production, 6,7 leukocyte adherence to vascular endothelial cells, 8 -11 and impairment of macrophage function.…”

Gene expression of estrogen receptor-alpha in orbital fibroblasts in Graves’ ophthalmopathy

“…In the groups treated with 10 nM and 100 nM DEX, ERA gene expression was, respectively, 85% higher and 74% lower, than in the control group, with receptor gene expression being significantly lower in the group treated with 100 nM than in the group treated with 10 nM DEX (Figure 2). Estrogen receptor in Graves' ophthalmopathy autoimmune diseases (14). Although still controversial, the immunosuppressive role of estrogen in autoimmune diseases has been regarded as important (14).…”

“…Estrogen receptor in Graves' ophthalmopathy autoimmune diseases (14). Although still controversial, the immunosuppressive role of estrogen in autoimmune diseases has been regarded as important (14). Thus, among the nuclear receptors possibly involved in GO, there are ERs, which have been associated with inflammatory processes, whether they are autoimmune or not (5,8).…”

“…However, the expression of ERA in orbital fibroblasts from a patient with GO, as seen in this study, has not been previously reported. Assuming estrogen involvement in GO development, it seems more likely that its immune modulatory effect is mediated through these cells, rather than directly through inflammatory cells, which express low levels of ER (14).…”