Estrogen Regulates CCR Gene Expression and Function in T Lymphocytes

Abstract

Estrogen has been implicated in the observed female bias in autoimmune diseases. However, the mechanisms behind this gender dimorphism are poorly defined. We have previously reported that in vivo T cell trafficking is gender- and estrogen-dependent. Chemokine receptors are critical determinants of T cell homing and immune response. In this study, we show that the female gender is associated with increased CD4+ T cell CCR1-CCR5 gene and protein expression in mice. The increased CCR expression correlates with enhanced in vitro chemotaxis response to MIP-1β (CCL4). In vivo treatment of young oophorectomized and postmenopausal female mice with 17β-estradiol also increased CD4+ T cell CCR expression. Finally, 17β-estradiol enhances tyrosine phosphorylation in T cells stimulated with MIP-1α in a time-dependent manner. Our results indicate an important role of estrogen in determining T cell chemokine response that may help explain the increased susceptibility and severity of autoimmune diseases in females.