Oral administration of MOG۳۵–۵۵ ameliorates Experimental autoimmune encephalomyelitis by reduction of Th۱ and Th۱۷ immune responses

Background and aim: Multiple sclerosis (MS) is a demyelinating autoimmune disorder of the central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) has been widely used to determine the pathogenesis of the disease and evaluate new treatment strategies of MS such as induction of immune tolerance. Considering that oral exposure of protein antigens can lead to tolerance, we investigated the efficacy of oral administration of a myelin oligodendrocyte glycoprotein (MOG۳۵-۵۵) on control of EAE.Materials and method: Daily administration of MOG (۲۵۰μg/kg of body weight) in oral route was conducted till ۱۴ days’ post-immunization, while EAE-induced mice in the control group received phosphate buffer saline (PBS). Clinical parameters were daily assessed and also immunological and histological evaluations were performed after ۲۱ days post-immunizationResults: MOG significantly controlled clinical score, weight loss, and CNS inflammation and demyelination mainly through the modulation of T cell proliferation, and reduction of pro-inflammatory cytokines and transcription factors, including TNF-α, IFN-ɣ, IL-۱۷ and T-bet, and ROR-ɣt. MOG treatment also induced a high mRNA expression of Foxp۳ and GATA-۳ accompanied with upregulated levels of IL-۴ and TGF-β.Conclusion: The results showed that oral administration of MOG could efficiently control EAE development. Immunomodulatory mechanisms mainly include the induction of T regulatory cells and the suppression of pro-inflammatory properties. However, the extension of this knowledge to MS patients needs further preclinical studies.

کلیدواژه ها:

Multiple Sclerosis ، Autoimmune Experimental Encephalomyelitis ، Myelin Oligodendrocyte Glycoprotein