Abstract
Women have stronger immune responses to infections and vaccination than men. Paradoxically, the stronger immune response comes at a steep price, which is the high incidence of autoimmune diseases in women. The reasons why women have stronger immunity and higher incidence of autoimmunity are not clear. Besides gender, sex hormones contribute to the development and activity of the immune system, accounting for differences in gender-related immune responses. Both innate and adaptive immune systems bear receptors for sex hormones and respond to hormonal cues. This review focuses on the role of sex hormones particularly estrogen, in the adaptive immune response, in health, and autoimmune disease with an emphasis on systemic lupus erythematosus.
Highlights
From an evolutionary point of view, the paramount goal of all living organisms is to survive, reproduce and propagate the species
Blocking with the anti-estrogen ICI 172 180 led to increase in IFN-γ & IL-4 production from Teffs derived from cervical-cancer suggesting that estrogen receptor (ER) blockade could potentially restore certain Teff functions in tumors. These results showed that E2 and ERα are required for the Forkhead box P3 (FoxP3) expression and tumor-derived Treg and Teff function [102]
B lymphocyte stimulator (Blys) called B cell activating factor (BAFF) is a vital cytokine for survival and maturation of B cells, and elevated serum levels have been found in SLE patients [129]
Summary
From an evolutionary point of view, the paramount goal of all living organisms is to survive, reproduce and propagate the species. E2 suppressed IL-2 production in T cells from healthy women and increased the expression of Sp1 transcription factor and the cAMP response element modulator (CREM) transcriptional repressor [79, 80] These studies showed that estrogen has specific concentration- and receptor-subtype dependent effects on immune responses. Estrogen suppresses IL-17 and Th17 differentiation in mouse CD4 T cells by downregulating the RORγt transcription factor mRNA and protein expression This effect was mediated by an E2-activated complex of ERα and repressor of ER activity (REA) binding to three ERE half sites within the RORγt promoter [88]. These studies indicate differential tissue-specific effects of estrogen on the immune response. It has been known for a long time that estrogen enhances humoral responses, enhances B cell differentiation and immunoglobulin (Ig) production [112, 113]
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