Central and peripheral myeloid-derived suppressor cell-like cells are closely related to the clinical severity of multiple sclerosis

Abstract

Multiple sclerosis (MS) is a highly heterogeneous demyelinating disease of the central nervous system (CNS) that needs for reliable biomarkers to foresee disease severity. Recently, myeloid-derived suppressor cells (MDSCs) have emerged as an immune cell population with an important role in MS. The monocytic-MDSCs (M-MDSCs) share the phenotype with Ly-6Chi-cells in the MS animal model, experimental autoimmune encephalomyelitis (EAE), and have been retrospectively related to the severity of the clinical course in the EAE. However, no data are available about the presence of M-MDSCs in the CNS of MS patients or its relation with the future disease aggressiveness. In this work, we show for the first time cells exhibiting all the bona-fide phenotypical markers of M-MDSCs associated with MS lesions, whose abundance in these areas appears to be directly correlated with longer disease duration in primary progressive MS patients. Moreover, we show that blood immunosuppressive Ly-6Chi-cells are strongly related to the future severity of EAE disease course. We found that a higher abundance of Ly-6Chi-cells at the onset of the EAE clinical course is associated with a milder disease course and less tissue damage. In parallel, we determined that the abundance of M-MDSCs in blood samples from untreated MS patients at their first relapse is inversely correlated with the Expanded Disability Status Scale (EDSS) at baseline and after a 1-year follow-up. In summary, our data point to M-MDSC load as a factor to be considered for future studies focused on the prediction of disease severity in EAE and MS.

Causal association between the peripheral immunity and the risk and disease severity of multiple sclerosis

“…In the experimental autoimmune encephalomyelitis (EAE) model, MDSCs can trigger T cell apoptosis to suppress inflammation and boost recovery of EAE symptoms ( 52 ). Similarly, the abundance of Monocytic MDSC in blood samples from untreated MS patients at the time of first relapse had a negative correlation with the EDSS at baseline and after one-year follow-up ( 53 ), underscoring the need for dynamic MDSC monitoring in the development of MS.…”

Intracerebellar injection of monocytic immature myeloid cells prevents the adverse effects caused by stereotactic surgery in a model of cerebellar neurodegeneration

“…For this reason, the transplantation of IMCs could offer a neuroprotective strategy worth contemplating, especially if we consider that their immunoregulatory potency is acquired and enhanced by inflammation [ 79 ]. In addition, it has very recently been shown that MDSCs exert an important immunosuppressive effect over both activated T and B cells [ 80 ]. For all these reasons we did not apply any type of immunosuppressive treatment.…”

The Influence of Myeloid-Derived Suppressor Cell Expansion in Neuroinflammation and Neurodegenerative Diseases

“…Among the fifteen studies investigating the MDSC expansion in MS, two were conducted in human subjects [43,44], three used both human subjects and a mouse model [45][46][47], eight were performed in a mouse model [15,[48][49][50][51][52][53][54], and two in vitro, using MDSCs isolated from MS patients or a mouse model of MS [55,56]. The investigations on MDSC-targeting treatment were carried out in murine models or in vitro cells collected from MS patients or EAE animals.…”

“…In RRMS, both M-and PMN-MDSC subsets are increased during the relapse with respect to the remitting phase and healthy subjects [43][44][45]47]. Moreover, the greater the number of M-MDSCs in the relapse phase, the faster the recovery.…”

“…Moreover, the greater the number of M-MDSCs in the relapse phase, the faster the recovery. Indeed, a higher percentage of M-MDSCs during the relapse leads to a faster and full recovery, while a low percentage of M-MDSCs in relapse results in partial recovery, suggesting that M-MDSC expansion during the active phase influences disease progression [47,52]. M-MDSC depletion results in the increase in CD4+T and CD8+T cells and auto-reactive T cells, which exacerbate the demyelination [48].…”