Monocytic-myeloid-derived suppressor cells (M-MDSCs) have emerged as a new immune cell population with a crucial role in regulating the inflammatory response in immune-related disorders, including multiple sclerosis (MS). Recent data from our group have shown that the proportion of splenic M-MDSCs is related to the severity of the clinical course and tissue damage extent in a murine model of MS. Furthermore, we have observed that the abundance of M-MDSCs (Ly-6Chigh-cells) in the peripheral blood at the onset of the symptoms can be inversely correlated with the severity of the future clinical course as well as with demyelination and axonal damage. Interestingly, it has also been observed a direct correlation between the high number of Ly-6Chi-cells and the higher density of Arg-I+ (M-MDSCs) and NG2+ cells (OPCs) associated to areas of de-(re)myelination in the spinal cord at the peak of the disease. Our observations show that M-MDSCs peripheral load at the onset of the symptoms may play a role as a putative bioindicator not only of a milder severity of the future clinical course but also of a less damaged CNS prone to spontaneous remyelination.
Given these results and the lack of information about the presence of M-MDSCs in human tissue, we wonder if their abundance and distribution in MS lesions might also help us to shed more light on the variability in the clinical course of MS patients.
M-MDSC distribution was analysed in CNS samples from 30 MS patients with different aggressiveness of their clinical courses and 6 controls. The characterization of M-MDSCs was performed by immunohistochemistry using the following markers: CD11b, HLA-DR, CD14 and CD15.
For the first time, we have identified CD11b+CD14+CD15-HLA-DR-/low-cells as putative M-MDSCs in the CNS of PPMS and SPMS patients, which were mainly circumscribed to areas with a spontaneous capacity of remyelination, i.e within the plaque of the active lesions and in the periplaque of chronic-active lesions. Remarkably, the abundance of M-MDSCs in the aforementioned high inflammatory areas showed a significant direct correlation with the disease duration.
These data indicate that the higher density of M-MDSCs in regions with spontaneous capacity to be repaired, the lesser severe clinical course according to the disease length. In sum, our data give more insights about M-MDSCs as putative biomarker of the clinical course severity as well as the degree of histopathological damage in the CNS of MS patients.