Clinical Reviews in Allergy & Immunology

, Volume 40, Issue 1, pp 66–73 | Cite as

Estrogen Receptors in Immunity and Autoimmunity

  • Melissa Cunningham
  • Gary Gilkeson


Due to the female predominance of autoimmune diseases, the role of gender and sex hormones in the immune system is of long-term interest. Estrogen's primary effects are mediated via estrogen receptors alpha and beta (ER α/β) that are expressed on most immune cells. ERs are nuclear hormone receptors that can either directly bind to estrogen response elements in gene promoters or serve as cofactors with other transcription factors (i.e., NFkB/AP1). Cytoplasmic ER and membrane associated ER impact specific kinase signaling pathways. ERs have prominent effects on immune function in both the innate and adaptive immune responses. Genetic deficiency of ERα in murine models of lupus resulted in significantly decreased disease and prolonged survival, while ERβ deficiency had minimal to no effect in autoimmune models. The protective effect of ERα in lupus is multifactoral. In arthritis models, ERα agonists appears to mediate a protective effect. The modulation of ERα function appears to be a potential target for therapy in autoimmunity.


Estrogen receptors Autoimmunity Gender prevalence 



This work was supported by a Merit Review Award and a REAP award from the Veterans Administration Medical Research Service.


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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Medical Research Service, Ralph H. Johnson VAMC and the Department of Medicine, Division of RheumatologyMedical University of South CarolinaCharlestonUSA

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