The multi-faceted influences of estrogen on lymphocytes: toward novel immuno-interventions strategies for autoimmunity management.
Early studies of the immune system disclosed that, generally, females exhibit stronger responses to a variety of antigens than males. Perhaps as a result of this response, women are more prone to developing autoimmune diseases than men. Yet, the precise cellular and molecular mechanisms remain under investigation. Recently, interferon-gamma and the related pro-inflammatory interleukin-12 were found to be under effects of sex steroid hormones, with potential implications in regulating immune cells and autoimmune responses. In B lymphocytes, functional binding sites for estrogen receptors were identified in the promoter of the gene encoding activation-induced deaminase, an enzyme required for somatic hypermutation, and class-switch recombination. The observation that estrogen exerts direct impacts on antibody affinity-maturation provides a potential mechanism that could account for generating pathogenic high-affinity auto-antibodies. Further deciphering the multi-faceted influences of sex hormones on the responsiveness of immune cells could lead to novel therapeutic interventions for autoimmunity management.
Karpuzoglu
Ebru
E
Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Disease, Virginia-Maryland Regional College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA.
Zouali
Moncef
M
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D015551:Autoimmunity / Q000187:drug effects / Q000235:genetics; D004967:Estrogens / Q000276:immunology* / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology*
D001323:Autoantibodies; D004967:Estrogens; D018664:Interleukin-12; D007371:Interferon-gamma