Estrogen affects the differentiation and function of splenic monocyte-derived dendritic cells from normal rats.
OBJECTIVE
To explore the mechanism resulting in the preventive effect of estrogen on experimental autoimmune encephalomyelitis (EAE), which is an animal model for multiple sclerosis (MS), and examine if estrogen can affect the immune response in EAE at dendritic cell (DC) level.


METHODS
Flow cytometry was used to reveal the surface marker expression. 3H-thymidine incorporation was applied to examine the cellular proliferation. Levels of anti-myelin basic protein (MBP)(68-86) antibody and cytokines were determined by enzyme-linked immunospot and ELISA, respectively.


RESULTS
17beta-estradiol (E2) could dose-dependently accelerate the differentiation process of DCs by up-regulating CD11c, B7-2 and CD40 expressions, but exert no effect on its antigen presentation ability. MBP-specific T cells cocultured with E2-treated DCs (E2-DC) produced more IL-10 and less IFN-gamma in the supernatant than those without E2 pretreatment (ctr-DC). In contrast to ctr-DC, E2-DC, if injected i.v. into EAE rats on day 5 post immunization, could initiate antigen nonspecific hyper-responsivity in T cells in terms of enhanced proliferation and cytokine secretion of mononuclear cells in LN, but suppressed antibody secretion from splenocytes.


CONCLUSIONS
These results suggest that estrogen can affect the differentiation and function of DCs, which leads T cells switching to Th2 secretion. This may account partly for the protective effect of estrogen on EAE.
Zhang
Qing-hong
QH
Department of Physiology, Institute of Basic Medical Science, Xi'an 710032, China. z_qinghong@hotmail.com
Cao
Jun
J
Hu
Yu-zhen
YZ
Huang
Yan-hong
YH
Lü
Shun-yan
SY
Wei
Geng-ze
GZ
Zhao
Yu-feng
YF
D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects; D051940:B7-2 Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004958:Estradiol / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000473:pathology; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000473:pathology; D018418:Th2 Cells / Q000378:metabolism*
D051940:B7-2 Antigen; D039521:CD11c Antigen; D019013:CD40 Antigens; D004676:Myelin Basic Protein; D010446:Peptide Fragments; C079716:myelin basic protein 68-88; D016753:Interleukin-10; D004958:Estradiol; D007371:Interferon-gamma