title: Altered Expression of Specific Transcription Factors of Th17 (RORγt, RORα) and Treg Lymphocytes (FOXP3) by Peripheral Blood Mononuclear Cells from Patients with Multiple Sclerosis.
abstract: The imbalance in Th17/Treg cell-related responses plays an important role in the pathogenesis of multiple sclerosis (MS). The development of Th17- and Treg cells is regulated by specific transcription factors-RORγt and RORα-and FOXP3, respectively. The aim was to determine the expression of RORγt, RORα, and FOXP3 in peripheral blood mononuclear cells (PBMCs) from MS patients following in vitro stimulation. The PBMCs from 22 MS patients and 20 healthy subjects were cultured in the presence of 10 μg/ml MOG, 10 μg/ml PHA, or without stimulation. The PBMCs were incubated at 37 °C for 24 h, and then the messenger RNA (mRNA) expression of RORγt, RORα, and FOXP3 was determined by real-time PCR. The expression of RORγt and RORα was increased in non-stimulated, MOG-stimulated, and PHA-stimulated PBMCs from MS patients in comparison with same cultures from the healthy group (P < 0.01, P < 0.01, and P < 0.02 for RORγt; P < 0.001, P < 0.001, and P < 0.05, for RORα, respectively). The FOXP3 expression in non-stimulated PBMCs from MS patients was significantly lower than that in equal culture from healthy subjects (P < 0.05). There were no significant differences between healthy subjects and MS patients regarding the expression of FOXP3 mRNA by MOG-stimulated and PHA-stimulated PBMCs. These results showed an imbalance in Th17/Treg cells at transcription factor levels with a deviation toward Th17 cell in MS. The correction of Th17/Treg balance at transcription levels should be considered to design novel therapeutic strategies for MS treatment.
authors.affiliation: Neurology Research Center, Department of Neurology, Kerman University of Medical Sciences, Kerman, Iran.|Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Etesam
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.|Department of Laboratory Sciences, Para-Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nemati
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Mohammad-Amin
authors.initials: MA
authors.lastname: Ebrahimizadeh
authors.affiliation: Neurology Research Center, Department of Neurology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Hossain-Ali
authors.initials: HA
authors.lastname: Ebrahimi
authors.affiliation: Department of Immunology, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Hossain
authors.initials: H
authors.lastname: Hajghani
authors.affiliation: Department of Biochemistry, Medical School, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Tahereh
authors.initials: T
authors.lastname: Khalili
authors.affiliation: Islamic Azad University of Flavarjan, Isfahan, Iran.
authors.forename: Razieyeh
authors.initials: R
authors.lastname: Frootan
authors.affiliation: Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
authors.forename: Nahid
authors.initials: N
authors.lastname: Zinoddini
authors.affiliation: Department of Immunology, Medical School, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Jafarzadeh14@yahoo.com.
authors.forename: Abdollah
authors.initials: A
authors.lastname: Jafarzadeh
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000378:metabolism; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000378:metabolism*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics / Q000378:metabolism*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539738:RORA protein, human
keywords: FOXP3; Multiple sclerosis; RORα; RORγt; Th17; Transcription factors; Treg