pSTAT1, pSTAT3, and T-bet expression in peripheral blood mononuclear cells from relapsing-remitting multiple sclerosis patients correlates with disease activity.
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, and it is considered to be a T helper 1 (Th1) cell-mediated autoimmune disease. T-bet has been identified as a key transcription factor for the development of Th1 cells and the induction of interferon (IFN)-gamma production. T-bet is induced during T-cell activation by the IFN-gamma signal transducer and activator of transcription (STAT)-1 signalling pathway. In this study we found an up-regulation of T-bet and pSTAT1 in peripheral blood CD4+ and CD8+ T cells and monocytes from relapsing-remitting MS patients in relapse compared with patients in remission and with healthy subjects. The increased expression of pSTAT1 strongly correlated with T-bet expression in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of IFN-gamma by peripheral blood mononuclear cells (PBMCs). pSTAT3 was also up-regulated in CD4+ and CD8+ cells and monocytes from patients in relapse and was associated with an increased production of interleukin (IL)-10 but not of IL-6. pSTAT1, pSTAT3, and T-bet expression strongly correlated with Gd-DTPA-enhanced lesions on brain and spinal cord magnetic resonance imaging. Our data show for the first time that there is an up-regulation of type 1 immunity-correlated transcription factors such as STAT1 and T-bet in peripheral blood subpopulations of MS patients in the active phase of disease. The evaluation of T-bet and pSTAT1 expression in peripheral blood CD4+, CD8+ T cells and monocytes could be used as a marker of disease activity in relapsing-remitting MS.
Frisullo
Giovanni
G
Institute of Neurology, Department of Neuroscience, Catholic University, Rome, Italy.
Angelucci
Francesco
F
Caggiula
Marcella
M
Nociti
Viviana
V
Iorio
Raffaele
R
Patanella
Agata Katia
AK
Sancricca
Cristina
C
Mirabella
Massimiliano
M
Tonali
Pietro Attilio
PA
Batocchi
Anna Paola
AP
D000328:Adult; D000704:Analysis of Variance; D015703:Antigens, CD / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015870:Gene Expression / Q000502:physiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000097:blood / Q000473:pathology*; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
D015703:Antigens, CD; D016207:Cytokines; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor