Short-term effect of IFN-β therapy on the expression of IL23A, FOXP3 and
IL10 in CD4+ and CD25+ T cells of MS patients
Abstract
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. By the time, the disease
progresses, and its outcomes become unbearable for the patient. IFN-β
has been used in MS therapy for many years. It slows down the disease
progression, also reduces disease symptoms by targeting T cells. Yet, a
considerable portion of the patient has experienced no therapeutic
response to IFN-β. Therefore, 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 IL10, IL23A and FOXP3
genes on the therapeutic response to MS after IFN-β administration.
PBMCs were extracted from blood samples to isolate CD4+ and CD25+ T
cells. Cytotoxicity assays were performed on each cell type for
determining optimum drug concentration. Then cells were cultured again
and determined drug concentration was administered to the cells to
measure gene expressions with RT-PCR. At the end of the study, 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, which
both were statistically significant.