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Adaptive human immunity drives remyelination in a mouse model of demyelination

View Article: PubMed Central - PubMed

ABSTRACT

The factors that determine whether remyelination fails or succeeds in multiple sclerosis remain unknown. By grafting lymphocytes from patients into demyelinated lesions in mice, El Behi, Sanson et al. show that lymphocytes differ in their ability to induce remyelination. Unravelling the basis of this heterogeneity reveals prerequisites for efficient myelin repair.

No MeSH data available.


Related in: MedlinePlus

Multiple sclerosis patient lymphocyte supernatants induce an increase in the M1/M2 ratio of microglia. Schematic of the MIG activation assay in response to lymphocyte supernatants (A). Healthy donor (HD) or multiple sclerosis (MS) lymphocytes were activated during 72 h with anti CD2/CD3/CD28 antibodies and the supernatants were collected. Murine microglia cells were next exposed to culture media (CT) (B, E and H), healthy donor (C, F and I) or multiple sclerosis patient (D, G and J) lymphocyte supernatants over 24 h. M1 and M2 cells were labelled using iNOS (B–D, H–J) and IGF-1 (B–G), respectively. The iNOS+ IGF-1+ cells ratio was calculated for the CT (n = 7), healthy donors (n = 11) and multiple sclerosis (n = 27) groups (K). Each experiments was performed in triplicate. ***P < 0.001, Kruskal-Wallis and Dunn’s multiple comparison test. Scale bar = 100 µm.
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awx008-F2: Multiple sclerosis patient lymphocyte supernatants induce an increase in the M1/M2 ratio of microglia. Schematic of the MIG activation assay in response to lymphocyte supernatants (A). Healthy donor (HD) or multiple sclerosis (MS) lymphocytes were activated during 72 h with anti CD2/CD3/CD28 antibodies and the supernatants were collected. Murine microglia cells were next exposed to culture media (CT) (B, E and H), healthy donor (C, F and I) or multiple sclerosis patient (D, G and J) lymphocyte supernatants over 24 h. M1 and M2 cells were labelled using iNOS (B–D, H–J) and IGF-1 (B–G), respectively. The iNOS+ IGF-1+ cells ratio was calculated for the CT (n = 7), healthy donors (n = 11) and multiple sclerosis (n = 27) groups (K). Each experiments was performed in triplicate. ***P < 0.001, Kruskal-Wallis and Dunn’s multiple comparison test. Scale bar = 100 µm.

Mentions: Lymphocyte supernatants from multiple sclerosis patients, healthy donors or fresh culture media [control condition (CT)] were added to MIGs (Fig. 2A). After 24 h, cells were fixed and stained for two markers of MIG activation: iNOS, which labels the M1 state (Fig. 2B–D, H–J), and IGF-1, a marker of the M2 state (Fig. 2B–G). We evaluated the ratio of iNOS+ cells to IGF-1+ (Fig. 2K) and showed that healthy donor lymphocyte supernatants did not change the M1/M2 ratio compared to control conditions, while multiple sclerosis lymphocyte supernatants induced a significant shift towards an M1 phenotype leading to an increase of the M1/M2 ratio. These results were further confirmed using arginase-1 (Arg-1), another M2 marker (Supplementary Fig. 3).Figure 2


Adaptive human immunity drives remyelination in a mouse model of demyelination
Multiple sclerosis patient lymphocyte supernatants induce an increase in the M1/M2 ratio of microglia. Schematic of the MIG activation assay in response to lymphocyte supernatants (A). Healthy donor (HD) or multiple sclerosis (MS) lymphocytes were activated during 72 h with anti CD2/CD3/CD28 antibodies and the supernatants were collected. Murine microglia cells were next exposed to culture media (CT) (B, E and H), healthy donor (C, F and I) or multiple sclerosis patient (D, G and J) lymphocyte supernatants over 24 h. M1 and M2 cells were labelled using iNOS (B–D, H–J) and IGF-1 (B–G), respectively. The iNOS+ IGF-1+ cells ratio was calculated for the CT (n = 7), healthy donors (n = 11) and multiple sclerosis (n = 27) groups (K). Each experiments was performed in triplicate. ***P < 0.001, Kruskal-Wallis and Dunn’s multiple comparison test. Scale bar = 100 µm.
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awx008-F2: Multiple sclerosis patient lymphocyte supernatants induce an increase in the M1/M2 ratio of microglia. Schematic of the MIG activation assay in response to lymphocyte supernatants (A). Healthy donor (HD) or multiple sclerosis (MS) lymphocytes were activated during 72 h with anti CD2/CD3/CD28 antibodies and the supernatants were collected. Murine microglia cells were next exposed to culture media (CT) (B, E and H), healthy donor (C, F and I) or multiple sclerosis patient (D, G and J) lymphocyte supernatants over 24 h. M1 and M2 cells were labelled using iNOS (B–D, H–J) and IGF-1 (B–G), respectively. The iNOS+ IGF-1+ cells ratio was calculated for the CT (n = 7), healthy donors (n = 11) and multiple sclerosis (n = 27) groups (K). Each experiments was performed in triplicate. ***P < 0.001, Kruskal-Wallis and Dunn’s multiple comparison test. Scale bar = 100 µm.
Mentions: Lymphocyte supernatants from multiple sclerosis patients, healthy donors or fresh culture media [control condition (CT)] were added to MIGs (Fig. 2A). After 24 h, cells were fixed and stained for two markers of MIG activation: iNOS, which labels the M1 state (Fig. 2B–D, H–J), and IGF-1, a marker of the M2 state (Fig. 2B–G). We evaluated the ratio of iNOS+ cells to IGF-1+ (Fig. 2K) and showed that healthy donor lymphocyte supernatants did not change the M1/M2 ratio compared to control conditions, while multiple sclerosis lymphocyte supernatants induced a significant shift towards an M1 phenotype leading to an increase of the M1/M2 ratio. These results were further confirmed using arginase-1 (Arg-1), another M2 marker (Supplementary Fig. 3).Figure 2

View Article: PubMed Central - PubMed

ABSTRACT

The factors that determine whether remyelination fails or succeeds in multiple sclerosis remain unknown. By grafting lymphocytes from patients into demyelinated lesions in mice, El Behi, Sanson et al. show that lymphocytes differ in their ability to induce remyelination. Unravelling the basis of this heterogeneity reveals prerequisites for efficient myelin repair.

No MeSH data available.


Related in: MedlinePlus