Author Of 2 Presentations
P0781 - Myeloid-Derived Suppressor Cells associated to a mild disease course are good bioindicators of a higher remyelinating capability in Multiple Sclerosis (ID 1650)
Abstract
Background
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) in which areas of demyelination are the main histopathological hallmark. Some of these areas are spontaneously remyelinated by oligodendrocyte precursor cells (OPCs), a process in which regulatory immune cells are important promoting factors. Myeloid-derived suppressor cells (MDSCs) are regulatory immune cells that promote OPC proliferation, survival and differentiation. Previous work of our group in the murine model of MS, Experimental Autoimmune Encephalomyelitis (EAE), showed that the peripheral load of MDSCs at the onset of symptoms is inversely correlated with the severity of the clinical course and the degree of demyelination, and directly correlated with the density of infiltrated MDSCs and OPCs in the demyelinated plaque and the adjacent periplaque of the spinal cord lesions, respectively.
Objectives
Due to the fact that the mobilization of OPCs towards the inflammatory lesion area is crucial for myelin repair after a demyelinating insult, in the present work we interrogate whether the increase in OPC densities in EAE mice that have suffered a mild disease course could also be the consequence of greater proliferative activity during the inflammatory phase. Further, we will study whether MDSC peripheral load in the blood is a good bioindicator of this proliferative capacity as well as to a higher mature oligodendrocyte (OL) density associated to EAE demyelinated areas.
Methods
MDSCs were analyzed in the peripheral blood of each EAE mouse at onset of disease course. BrdU was i.p. injected since onset during three consecutive days. Animals were followed up till the day of maximal affectation and spinal cords were dissected out for the histopathology analysis of proliferating MDSCs and OPCs, and for OL distribution in association to areas of demyelination. A correlation analysis was carried out between blood MDSCs, the future disease severity, and the different histopathological parameters.
Results
We show that the higher MDSC content in the peripheral blood at the onset of the disease is associated to the higher density of proliferating MDSCs in the demyelinated plaque together with a higher density of proliferating OPCs in the adjacent periplaque at the peak of the disease. In contrast, MDSCs at onset of EAE is independent of the abundance of OLs in areas of demyelination. Interestingly, the presence of MDSCs in the inflamed tissue directly correlated with a higher OPC proliferation and OL preservation in the adjacent areas. Finally, the more aggressive clinical course in each animal is related to a dramatic decrease in both OPCs and OLs in the inflamed CNS.
Conclusions
Our data indicate that the predictive capacity of peripheral MDSC-based association to a milder disease course can be considered as a good bioindicator of a CNS prone to succeed in spontaneous remyelination.
P0782 - Myeloid-derived suppressor cells in progressive multiple sclerosis: important factors for clinical course severity (ID 1376)
Abstract
Background
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.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.
Presenter Of 1 Presentation
P0782 - Myeloid-derived suppressor cells in progressive multiple sclerosis: important factors for clinical course severity (ID 1376)
Abstract
Background
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.
Objectives
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.
Methods
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.
Results
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.
Conclusions
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.