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.

NK Cell Levels Correlate with Disease Activity in Patients with Multiple Sclerosis on Ocrelizumab/Rituximab Therapy

“…Based on the assumption that pregnancy is protective against disease activity while postpartum increases the risk of MS reactivation [ 16 ], our data would be in line with the literature, confirming the protective effect of a higher percentage of NK cells on MS. Considering these data, we could confirm the hypothesis that NK cells play a role in the regulation of immunotolerance and thus in the pathogenesis of MS, as previously postulated [ 5 ], and that their alteration may indeed modify the course of the disease.…”

“…Indeed, NK cells also appear to be involved in the control of the effector functions of T cells: the reduced immunoregulatory function of these cells could be one of the driving forces in the pathogenesis of autoimmune diseases, such as MS. To date, few studies have explored the effects of anti-CD20 drugs on NK cells in MS patients, and the available results are conflicting [ 4 ]. It has recently been found that some therapies used in MS, such as Natalizumab, Fingolimod, Interferon alpha, and autologous marrow transplantation, increase the number of NK cells [ 5 ]. In addition, therapies, including Glatiramer acetate, Vitamin D3, Dimethylfumarate, Monomethylfumarate, Natalizumab, Ocrelizumab, and IFN-β, have been shown to increase the biological activity of NK cells [ 6 ].…”

People with Primary Progressive Multiple Sclerosis Have a Lower Number of Central Memory T Cells and HLA-DR+ Tregs

“…NK and NKT cells have a very important role in immune homeostasis, as they express inhibitory and/or activating receptors that allow these cells to identify potential hazardous target cells and kill them, including activated autoreactive T cells [30,31]. The most immature NK cells, CD56 bright , are described to act mostly through cytokine production, while CD56 dim mediate their cytotoxicity in a contact-dependent manner.…”

Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment

“…The pathogenesis of MS increases with CD56 bright NK cells, as these cells promote intensive secretion of cytokines (INF-γ, TNF-α, and IL-10) and adaptive immune response, whereas CD56 dim is closely associated with cytolysis. These immunoregulatory functions have been reported in clinical trials in patients (Kucuksezer et al, 2021;Ahmadi et al, 2022). Some drugs, such as daclizumab, participate in the control of MS because of their association with the inhibition of the marker CD56 brigh (Ruiz et al, 2019).…”