Dendritic cells exposed to estrogen in vitro exhibit therapeutic effects in ongoing experimental allergic encephalomyelitis.
Immunomodulatory effects of estrogen have been demonstrated by clinical and experimental observations, but the mechanisms by which estrogen exhibits the effects remain to be defined. One possible mechanism by which estrogen inhibits the development of experimental allergic encephalomyelitis (EAE), a commonly used model of multiple sclerosis (MS) in humans, is over the functions of dendritic cells (DC). Here, we describe that splenic DC from Lewis rats obtained on day 12 post-immunization (p.i.) with myelin basic protein (MBP) encephalitogenic peptide 68-86+Freund's complete adjuvant (FCA), after being exposed in vitro 17beta-estradiol, exhibited therapeutic effects on acute EAE when injected subcutaneously on day 5 p.i. Blood mononuclear cells (MNC) were isolated from thus treated rats on day 12 p.i. Administration of estrogen-exposed DC prevented the expansion of CD4+ T cells and increased proportions of regulatory T cells producing IL-10 and CD4+CD28- suppressor T cells, accompanied with increased IL-10 and IFN-gamma, and reduced TNF-alpha production. Infiltrates of CD68+ macrophages within the central nervous system and MBP 68-86-induced T cell proliferation were inhibited in rats injected with estrogen-exposed DC compared to rats injected with naive DC. Estrogen up-regulated the expression of indoleamine 2,3-dioxygenase, which promotes tolerogenic properties of DC. The results suggest that in vitro exposure of DC to estrogen modulates DC functions and results in a therapeutic effect of DC.
Division of Neuroimmunology, Neurotec Department, Karolinska Institute, Alfred Nobels Alle 10, SE 141 83, Stockholm, Sweden.
Asa
A
Pettersson
Carolina
C
Ciumas
Vadim
V
Chirsky
Hans
H
Link
Yu-Min
YM
Huang
Bao-Guo
BG
Xiao
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation*; D016503:Drug Delivery Systems / Q000379:methods; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000628:therapy*; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006168:Guinea Pigs; D007279:Injections, Subcutaneous; D051381:Rats; D011917:Rats, Inbred Lew
D000276:Adjuvants, Immunologic; D004958:Estradiol