A putative mechanism on remission of multiple sclerosis during pregnancy: estrogen-induced indoleamine 2,3-dioxygenase by dendritic cells.
The basis for the reduced relapse rate of multiple sclerosis (MS) during pregnancy remains unexplained but, if defined, could create novel treatment options. Estrogen constitutes one candidate molecule, but the mechanism by which estrogen may affect MS during pregnancy is unclear. In this study, we used monocyte-derived dendritic cells (DCs) from MS patients to explore the estrogen (17-beta-estradiol)-related pathway of immune modulation. Estrogen induced the expression of indoleamine 2,3-dioxygenase (IDO) on DCs, limiting T-cell proliferation and both Th1 and Th2 cytokine production. The suppression of T-cell proliferation mediated by estrogen-exposed DCs was partly abolished by the IDO-inhibitor, 1-methyl-dl-tryptophan, indicating that estrogen-exposed DCs induced IDO-dependent T-cell suppression. Our data support the hypothesis that the change in the clinical course of MS observed in pregnancy may be related to the estrogen-DC-IDO axis, which could represent a novel target for MS therapy.
Zhu
W H
WH
Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
Lu
C Z
CZ
Huang
Y M
YM
Link
H
H
Xiao
B G
BG
D000328:Adult; D002455:Cell Division / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism; D011247:Pregnancy; D011248:Pregnancy Complications / Q000276:immunology* / Q000378:metabolism; D012075:Remission, Spontaneous; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology
D016207:Cytokines; D004967:Estrogens; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase