The multi-faceted influences of estrogen on lymphocytes: toward novel immuno-interventions strategies for autoimmunity management

Clin Rev Allergy Immunol. 2011 Feb;40(1):16-26. doi: 10.1007/s12016-009-8188-0.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoantibodies / immunology
  • Autoimmune Diseases / immunology*
  • Autoimmunity / drug effects
  • Autoimmunity / genetics
  • Estrogens / immunology*
  • Estrogens / pharmacology
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-12 / immunology
  • Lupus Erythematosus, Systemic / immunology
  • Lymphocytes / drug effects
  • Lymphocytes / immunology*


  • Autoantibodies
  • Estrogens
  • Interleukin-12
  • Interferon-gamma