TY - JOUR
T1 - Cutting edge
T2 - Estrogen drives expiansion of the CD4+CD25 + regulatory T cell compartment
AU - Polanczyk, Magdalena J.
AU - Carson, Bryan D.
AU - Subramanian, Sandhya
AU - Afentoulis, Michael
AU - Vandenbark, Arthur A.
AU - Ziegler, Steven F.
AU - Offner, Halina
PY - 2004/8/15
Y1 - 2004/8/15
N2 - 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.
AB - 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.
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U2 - 10.4049/jimmunol.173.4.2227
DO - 10.4049/jimmunol.173.4.2227
M3 - Article
C2 - 15294932
AN - SCOPUS:4043071317
SN - 0022-1767
VL - 173
SP - 2227
EP - 2230
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -