Interferon-beta changes the expression of IL10, IL23A and FOXP3 on
Multiple Sclerosis patients' T cells
Abstract
Aim of the Study: Multiple sclerosis (MS) is an autoimmune disorder
causing demyelination in axons. Available therapies target different
molecules, but not all have therapeutic effects on disease progression,
and this effect can only be seen after a long-time administration.
Interferon beta (IFN-β), an MS therapy for many years, slows down the
disease progression and reduces disease symptoms by targeting T cells.
Yet, a considerable portion of the patient has experienced no
therapeutic response to IFN-β. It is necessary to determine
disease-specific biomarkers which allow early diagnosis or treatment of
MS. Here, it was aimed to determine the effects of interleukin 10 (IL10)
and 23 (IL23A) as well as forkhead box P3 (FOXP3) genes on MS after
IFN-β therapy. Materials & Methods: Peripheral blood mononuclear cells
(PBMCs) were extracted to isolate CD4+ and CD25+ T cells. Cytotoxicity
assays were performed on each cell type for determining optimum drug
concentration. Then, cells were cultured and determined drug
concentration was administered to the cells to measure gene expressions
with RT-PCR. Results: It was found that the cytotoxic effect of IFN-β
was more efficient as the exposure time was expanded regardless of drug
concentration. Moreover, CD25+ T lymphocytes were more resistant to
IFN-β. IL23A was down-regulated, whereas FOXP3 was up-regulated at 48h
in CD4+ T cells. For CD25+ T cells, the graded increase of FOXP3 was
obtained while IL10 expression was gradually decreased throughout the
drug intake, significantly. Conclusion: Although considerable change in
expression was obtained, the long-term IFN-β effect on both genes and
cells should be determined by follow-up at least a year. Keywords: MS,
IFN-β, IL23A, FOXP3, IL10, T cells