Diversity of immune cell types in multiple sclerosis and its animal model: Pathological and therapeutic implications

Abstract

Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system with an autoimmune attack on the components of the myelin sheath and axons. The etiology of the disease remains largely unknown, but it is commonly acknowledged that the development of MS probably results from the interaction of environmental factors in conjunction with a genetic predisposition. Current therapeutic approaches can only ameliorate the clinical symptoms or reduce the frequency of relapse in MS. Most drugs used in this disease broadly suppress the functions of immune effector cells, which can result in serious side effects. Thus, new therapeutic methods resulting in greater efficacy and lower toxicity are needed. Toward this end, cellbased therapies are of increasing interest in the treatment of MS. Several immunoregulatory cell types, including regulatory Tcells, regulatory B cells, M2 macrophages, tolerogenic dendritic cells, and stem cells, have been developed as novel therapeutic tools for the treatment of MS. In this Review, we summarize studies on the application of these cell populations for the treatment of MS and its animal model, experimental autoimmune encephalomyelitis, and call for further research on applications and mechanisms by which these cells act in the treatment of MS.

Serum levels of Homocysteine, Vitamin B12 and Folate in Patients with Multiple Sclerosis: an Updated Meta-Analysis

“…Multiple sclerosis (MS) is a neuro-inflammatory disease of the central nervous system (CNS), often followed by progressive and irreversible neurological dysfunction [1,2]. It affects more than two million young individuals worldwide and imposes an enormous economic burden on the societies [3].…”

Modulating inflammation and neuroprotection in multiple sclerosis

“…Initially, MS was thought to be mediated by Th1 cells because of the observation that induction of EAE resulted in Th1 differentiation. Furthermore, mice deficient in Tbet (the transcription factor driving Th1 responses) or STAT4 (a transcription factor involved in IL‐12–mediated Th1 differentiation) are both resistant to EAE induction (Cheng et al, ). This idea was contradicted in studies showing that mice with genetic ablation of Th1 receptors maintained susceptibility to disease (Zhang et al, ).…”

“…This idea was contradicted in studies showing that mice with genetic ablation of Th1 receptors maintained susceptibility to disease (Zhang et al, ). The paradox was resolved by the discovery of IL‐23, a structurally related cytokine to IL‐12 and a driver of Th17 expansion (Cheng et al, ; Fletcher, Lalor, Sweeney, Tubridy, & Mills, ). Suppressing Th17 differentiation improves EAE disease course (McGeachy et al, ).…”

“…Furthermore GM‐CSF is a prerequisite for the development of disease in EAE (Ponomarev et al, ). On the other side of the spectrum, Th2 cells seem to be anti‐inflammatory, as observed in transgenic mice overexpressing GATA 3 (the transcription factor driving Th2 differentiation) that have delayed onset and severity of EAE (Cheng et al, ).…”

“…Additionally, T regulatory cells secrete immunosuppressive cytokines IL‐10, IL‐35, and TGF‐β and are depleted in the acute phase of EAE. Adoptive transfer or deletion experiments on T regulatory cells ameliorates disease severity of EAE (Cheng et al, ; Fletcher et al, ). Because of the heavy implication of T cells in MS pathogenesis, promising therapies may decrease autoreactive T cell development, alter these cells' pathogenic profile, or generate regulatory T cells (Segal & Shevach, ).…”