Cutting edge: Estrogen drives expiansion of the CD4+CD25 + regulatory T cell compartment

Magdalena J. Polanczyk, Bryan D. Carson, Sandhya Subramanian, Michael Afentoulis, Arthur A. Vandenbark, Steven F. Ziegler, Halina Offner

Research output: Contribution to journalArticlepeer-review

431 Scopus citations


CD4+CD25+ regulatory T cells are crucial to the maintenance of tolerance in normal individuals. However, the factors regulating this cell population and its function are largely unknown. Estrogen has been shown to protect against the development of autoimmune disease, yet the mechanism is not known. We demonstrate that estrogen (I 7-β-estradiol, E2) is capable of augmenting FoxP3 expression in vitro and in vivo. Treatment of naive mice with E2 increased both CD25+ cell number and FoxP3 expression level. Further, the ability of E2 to protect against autoimmune disease (experimental autoimmune encephalomyelitis) correlated with its ability to up-regulate FoxP3, as both were reduced in estrogen receptor α-deficient animals. Finally, E2 treatment and pregnancy induced FoxP3 protein expression to a similar degree, suggesting that high estrogen levels during pregnancy may help to maintain fetal tolerance. In summary, our data suggest E2 promotes tolerance by expanding the regulatory T cell compartment.

Original languageEnglish (US)
Pages (from-to)2227-2230
Number of pages4
JournalJournal of Immunology
Issue number4
StatePublished - Aug 15 2004

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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