Decreased FOXP3 levels in multiple sclerosis patients.
Autoimmune diseases such as multiple sclerosis (MS) may result from the failure of tolerance mechanisms to prevent expansion of pathogenic T cells. Our study is the first to establish that MS patients have abnormalities in FOXP3 message and protein expression levels in peripheral CD4+ CD25+ T cells (Tregs) that are quantitatively related to a reduction in functional suppression induced during suboptimal T-cell receptor (TCR) ligation. Of importance, this observation links a defect in functional peripheral immunoregulation to an established genetic marker that has been unequivocally shown to be involved in maintaining immune tolerance and preventing autoimmune diseases. Diminished FOXP3 levels thus indicate impaired immunoregulation by Tregs that may contribute to MS. Future studies will evaluate the effects of therapies known to influence Treg cell function and FOXP3 expression, including TCR peptide vaccination and supplemental estrogen.
Huan
Jianya
J
Department of Neurology, Oregon Health and Science University, Portland, Oregon, USA.
Culbertson
Nicole
N
Spencer
Leslie
L
Bartholomew
Richard
R
Burrows
Gregory G
GG
Chou
Yuan K
YK
Bourdette
Dennis
D
Ziegler
Steven F
SF
Offner
Halina
H
Vandenbark
Arthur A
AA
D000328:Adult; D015704:CD4 Antigens / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors; D005819:Genetic Markers / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015375:Receptors, Interleukin-2 / Q000276:immunology; D012016:Reference Values; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D005819:Genetic Markers; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2