The role of NK and NKT cells in the pathogenesis and improvement of multiple sclerosis following disease-modifying therapies

Abstract

Background: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) that T cells become autoreactive by recognizing CNS antigens. Both innate and adaptive immune systems are involved in the pathogenesis of MS. In recent years, the impact of innate immune cells on MS pathogenesis has received more attention. CD56bright NK cells, as an immunoregulatory subset of NK cells, can increase the production of cytokines that modulate adaptive immune responses, whereas CD56dim NK cells are more active in cytolysis functions. These two main subsets of NK cells may have different effects on the onset or progression of MS. Invariant NKT (iNKT) cells are other immune cells involved in the control of autoimmune diseases; however, variant NKT (vNKT) cells, despite limited information, could play a role in MS remission via an immunoregulatory pathway. Aim: We aimed to evaluate the influence of MS therapeutic agents on NK and NKT cells and NK cell subtypes. Materials and Methods: The possible mechanism of each MS therapeutic agent has been presented here, focusing on the effects of different disease-modifying therapies on the number of NK and NKT subtypes. Results: Expansion of CD56bright NK cells, reduction in the CD56dim cells, and enhancement in NKT cells are the more important innate immune cells alterations following the disease-modifying therapies. Conclusion: Expansion of CD56bright NK cells or reduction in the CD56dim cells has been associated with a successful response to different treatments in MS. iNKT and vNKT cells could have beneficial effects on MS improving. It seems that they are enhanced due to some of MS drugs, leading to disease improvement. However, a reduction in the number of NKT cells could be due to the adverse effects of some of MS drugs on the bone marrow.