Limits...
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 secretory pattern analysis revealed the cytokines correlated to OPC differentiation. All individuals used for the study were clustered in three subgroups: healthy donors and multiple sclerosis patients inducing an in vitro CNPase expression either above (HIGH, n = 13) or below (LOW, n = 13) the median value. A barycentric discriminant analysis (BADA) was performed (A) to define which variables were implementing variability in our dataset. A partial least square regression was performed on the dataset of patients according to a linear model (B) to determine which of the three blocks (lymphocyte composition, cytokine expression level and MIG activation) were correlated and could predict the value of the percentage of CNPase+ cells. Correlations between the different blocks and the percentage of CNPase+ cells were calculated (C). Boostrap ratios were calculated to evaluate the significance of each variable of each block allowing us to highlight cytokines that were not correlated (grey bars), significantly positively (purple bars) or significantly negatively (pink bars) correlated with the percentage of CNPase+ cells (D). The effect of CCL19 on OPC differentiation was evaluated in patients: MIG were exposed to lymphocyte (LT) supernatants (as described in Fig. 2) from LOW (E and F, n = 4) or HIGH (G and H, n = 5) with (F and H) or without (E and G) human recombinant CCL19 at 1 ng/ml. The M1/M2 ratio was calculated (I). Microglia-conditioned media pre-exposed to lymphocyte supernatants from LOW (J and K) or HIGH (L and M) subgroups, which were supplemented (K and M) or not (J and L) with CCL19 at 1 ng/ml were put on OPC (as described in Fig. 3). The proportion of CNPase+ cells was evaluated 72 h later (N). Each experiment was performed in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001. Bootstrap ratio (PLS) or paired two-tailed student’s t-test.
© Copyright Policy - cc-by-nc
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5382952&req=5

awx008-F6: Multiple sclerosis patient lymphocyte secretory pattern analysis revealed the cytokines correlated to OPC differentiation. All individuals used for the study were clustered in three subgroups: healthy donors and multiple sclerosis patients inducing an in vitro CNPase expression either above (HIGH, n = 13) or below (LOW, n = 13) the median value. A barycentric discriminant analysis (BADA) was performed (A) to define which variables were implementing variability in our dataset. A partial least square regression was performed on the dataset of patients according to a linear model (B) to determine which of the three blocks (lymphocyte composition, cytokine expression level and MIG activation) were correlated and could predict the value of the percentage of CNPase+ cells. Correlations between the different blocks and the percentage of CNPase+ cells were calculated (C). Boostrap ratios were calculated to evaluate the significance of each variable of each block allowing us to highlight cytokines that were not correlated (grey bars), significantly positively (purple bars) or significantly negatively (pink bars) correlated with the percentage of CNPase+ cells (D). The effect of CCL19 on OPC differentiation was evaluated in patients: MIG were exposed to lymphocyte (LT) supernatants (as described in Fig. 2) from LOW (E and F, n = 4) or HIGH (G and H, n = 5) with (F and H) or without (E and G) human recombinant CCL19 at 1 ng/ml. The M1/M2 ratio was calculated (I). Microglia-conditioned media pre-exposed to lymphocyte supernatants from LOW (J and K) or HIGH (L and M) subgroups, which were supplemented (K and M) or not (J and L) with CCL19 at 1 ng/ml were put on OPC (as described in Fig. 3). The proportion of CNPase+ cells was evaluated 72 h later (N). Each experiment was performed in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001. Bootstrap ratio (PLS) or paired two-tailed student’s t-test.

Mentions: To assess the contributions of each block of data to the remyelination process, we applied a hierarchical partial least square regression (PLS) (Fig. 6B), to evaluate their relative link to the percentage of CNPase+ cells. Network inference was performed by computing partial correlations and assessing their significance with GeneNet (Schaefer and Strimmer, 2005), which is particularly adapted to high dimensional data.


Adaptive human immunity drives remyelination in a mouse model of demyelination
Multiple sclerosis patient lymphocyte secretory pattern analysis revealed the cytokines correlated to OPC differentiation. All individuals used for the study were clustered in three subgroups: healthy donors and multiple sclerosis patients inducing an in vitro CNPase expression either above (HIGH, n = 13) or below (LOW, n = 13) the median value. A barycentric discriminant analysis (BADA) was performed (A) to define which variables were implementing variability in our dataset. A partial least square regression was performed on the dataset of patients according to a linear model (B) to determine which of the three blocks (lymphocyte composition, cytokine expression level and MIG activation) were correlated and could predict the value of the percentage of CNPase+ cells. Correlations between the different blocks and the percentage of CNPase+ cells were calculated (C). Boostrap ratios were calculated to evaluate the significance of each variable of each block allowing us to highlight cytokines that were not correlated (grey bars), significantly positively (purple bars) or significantly negatively (pink bars) correlated with the percentage of CNPase+ cells (D). The effect of CCL19 on OPC differentiation was evaluated in patients: MIG were exposed to lymphocyte (LT) supernatants (as described in Fig. 2) from LOW (E and F, n = 4) or HIGH (G and H, n = 5) with (F and H) or without (E and G) human recombinant CCL19 at 1 ng/ml. The M1/M2 ratio was calculated (I). Microglia-conditioned media pre-exposed to lymphocyte supernatants from LOW (J and K) or HIGH (L and M) subgroups, which were supplemented (K and M) or not (J and L) with CCL19 at 1 ng/ml were put on OPC (as described in Fig. 3). The proportion of CNPase+ cells was evaluated 72 h later (N). Each experiment was performed in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001. Bootstrap ratio (PLS) or paired two-tailed student’s t-test.
© Copyright Policy - cc-by-nc
Related In: Results  -  Collection

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

awx008-F6: Multiple sclerosis patient lymphocyte secretory pattern analysis revealed the cytokines correlated to OPC differentiation. All individuals used for the study were clustered in three subgroups: healthy donors and multiple sclerosis patients inducing an in vitro CNPase expression either above (HIGH, n = 13) or below (LOW, n = 13) the median value. A barycentric discriminant analysis (BADA) was performed (A) to define which variables were implementing variability in our dataset. A partial least square regression was performed on the dataset of patients according to a linear model (B) to determine which of the three blocks (lymphocyte composition, cytokine expression level and MIG activation) were correlated and could predict the value of the percentage of CNPase+ cells. Correlations between the different blocks and the percentage of CNPase+ cells were calculated (C). Boostrap ratios were calculated to evaluate the significance of each variable of each block allowing us to highlight cytokines that were not correlated (grey bars), significantly positively (purple bars) or significantly negatively (pink bars) correlated with the percentage of CNPase+ cells (D). The effect of CCL19 on OPC differentiation was evaluated in patients: MIG were exposed to lymphocyte (LT) supernatants (as described in Fig. 2) from LOW (E and F, n = 4) or HIGH (G and H, n = 5) with (F and H) or without (E and G) human recombinant CCL19 at 1 ng/ml. The M1/M2 ratio was calculated (I). Microglia-conditioned media pre-exposed to lymphocyte supernatants from LOW (J and K) or HIGH (L and M) subgroups, which were supplemented (K and M) or not (J and L) with CCL19 at 1 ng/ml were put on OPC (as described in Fig. 3). The proportion of CNPase+ cells was evaluated 72 h later (N). Each experiment was performed in quadruplicate. *P < 0.05, **P < 0.01, ***P < 0.001. Bootstrap ratio (PLS) or paired two-tailed student’s t-test.
Mentions: To assess the contributions of each block of data to the remyelination process, we applied a hierarchical partial least square regression (PLS) (Fig. 6B), to evaluate their relative link to the percentage of CNPase+ cells. Network inference was performed by computing partial correlations and assessing their significance with GeneNet (Schaefer and Strimmer, 2005), which is particularly adapted to high dimensional data.

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