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Adaptive human immunity drives remyelination in a mouse model of demyelination

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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 and healthy donor lymphocytes have a different secretory pattern. After in vitro activation of multiple sclerosis patient (MS, n = 27) or healthy donor (HD, n = 12) lymphocytes with anti-CD2/CD3/CD28 antibodies over 72 h, supernatants were collected. The level of expression of 72 cytokines was evaluated by Luminex (67 cytokines were detectable). Mean values for each tested cytokine were calculated. A heatmap was generated with colour coding representing the lower values in green, the higher values in red, and in grey the values close to the mean for each cytokine in healthy donor and multiple sclerosis conditions (A). Three cytokines were evidenced as differentially expressed between multiple sclerosis patient (n = 27) and healthy donor (n = 8) lymphocytes (B). *P < 0.05, **P < 0.01, Mann Whitney’s test. See also Supplementary Table 3.
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awx008-F4: Multiple sclerosis patient and healthy donor lymphocytes have a different secretory pattern. After in vitro activation of multiple sclerosis patient (MS, n = 27) or healthy donor (HD, n = 12) lymphocytes with anti-CD2/CD3/CD28 antibodies over 72 h, supernatants were collected. The level of expression of 72 cytokines was evaluated by Luminex (67 cytokines were detectable). Mean values for each tested cytokine were calculated. A heatmap was generated with colour coding representing the lower values in green, the higher values in red, and in grey the values close to the mean for each cytokine in healthy donor and multiple sclerosis conditions (A). Three cytokines were evidenced as differentially expressed between multiple sclerosis patient (n = 27) and healthy donor (n = 8) lymphocytes (B). *P < 0.05, **P < 0.01, Mann Whitney’s test. See also Supplementary Table 3.

Mentions: To assess potential differences between healthy donors and multiple sclerosis patients, we characterized immune cell composition by flow cytometry and evaluated their secretory profiles by a Luminex-based multiplex assay. While no substantial difference in the subtypes of T helper or B cells between multiple sclerosis patients and healthy donors was observed (Supplementary Table 3), we found that, among the 72 molecules analysed (Fig. 4A), three were statistically differentially expressed between multiple sclerosis patients and healthy donors: IL-7 and IL-20 where increased while CCL19 was downregulated in multiple sclerosis patients versus healthy donor conditions (Fig. 4B). Thus, even if lymphocyte subtype proportions do not differ between multiple sclerosis patients and healthy donors, their lymphocytes have a different intrinsic capacity to respond to stimulation.Figure 4


Adaptive human immunity drives remyelination in a mouse model of demyelination
Multiple sclerosis patient and healthy donor lymphocytes have a different secretory pattern. After in vitro activation of multiple sclerosis patient (MS, n = 27) or healthy donor (HD, n = 12) lymphocytes with anti-CD2/CD3/CD28 antibodies over 72 h, supernatants were collected. The level of expression of 72 cytokines was evaluated by Luminex (67 cytokines were detectable). Mean values for each tested cytokine were calculated. A heatmap was generated with colour coding representing the lower values in green, the higher values in red, and in grey the values close to the mean for each cytokine in healthy donor and multiple sclerosis conditions (A). Three cytokines were evidenced as differentially expressed between multiple sclerosis patient (n = 27) and healthy donor (n = 8) lymphocytes (B). *P < 0.05, **P < 0.01, Mann Whitney’s test. See also Supplementary Table 3.
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Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC5382952&req=5

awx008-F4: Multiple sclerosis patient and healthy donor lymphocytes have a different secretory pattern. After in vitro activation of multiple sclerosis patient (MS, n = 27) or healthy donor (HD, n = 12) lymphocytes with anti-CD2/CD3/CD28 antibodies over 72 h, supernatants were collected. The level of expression of 72 cytokines was evaluated by Luminex (67 cytokines were detectable). Mean values for each tested cytokine were calculated. A heatmap was generated with colour coding representing the lower values in green, the higher values in red, and in grey the values close to the mean for each cytokine in healthy donor and multiple sclerosis conditions (A). Three cytokines were evidenced as differentially expressed between multiple sclerosis patient (n = 27) and healthy donor (n = 8) lymphocytes (B). *P < 0.05, **P < 0.01, Mann Whitney’s test. See also Supplementary Table 3.
Mentions: To assess potential differences between healthy donors and multiple sclerosis patients, we characterized immune cell composition by flow cytometry and evaluated their secretory profiles by a Luminex-based multiplex assay. While no substantial difference in the subtypes of T helper or B cells between multiple sclerosis patients and healthy donors was observed (Supplementary Table 3), we found that, among the 72 molecules analysed (Fig. 4A), three were statistically differentially expressed between multiple sclerosis patients and healthy donors: IL-7 and IL-20 where increased while CCL19 was downregulated in multiple sclerosis patients versus healthy donor conditions (Fig. 4B). Thus, even if lymphocyte subtype proportions do not differ between multiple sclerosis patients and healthy donors, their lymphocytes have a different intrinsic capacity to respond to stimulation.Figure 4

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