Estrogen regulates CCR gene expression and function in T lymphocytes.
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-1beta (CCL4). In vivo treatment of young oophorectomized and postmenopausal female mice with 17beta-estradiol also increased CD4(+) T cell CCR expression. Finally, 17beta-estradiol enhances tyrosine phosphorylation in T cells stimulated with MIP-1alpha 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.
Mo
RuRan
R
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
Chen
Jun
J
Grolleau-Julius
Annabelle
A
Murphy
Hedwig S
HS
Richardson
Bruce C
BC
Yung
Raymond L
RL
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002460:Cell Line; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000378:metabolism*; D019743:Chemokines, CXC / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004967:Estrogens / Q000008:administration & dosage / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology; D008297:Male; D051379:Mice; D008806:Mice, Inbred AKR; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010052:Ovariectomy; D054398:Receptors, CCR4; D019713:Receptors, CCR5 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D012727:Sex Characteristics; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*
C515355:Ccr4 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D004967:Estrogens; D019402:Macrophage Inflammatory Proteins; D054398:Receptors, CCR4; D019713:Receptors, CCR5; D019707:Receptors, Chemokine