Adaptive human immunity drives remyelination in a mouse model of demyelination

Mohamed El Behi, Charles Sanson, Corinne Bachelin, Léna Guillot-Noël, Jennifer Fransson, Bruno Stankoff, Elisabeth Maillart, Nadège Sarrazin, Vincent Guillemot, Hervé Abdi, Isabelle Cournu-Rebeix, Bertrand Fontaine, Violetta Zujovic

Research output: Research - peer-reviewArticle

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Abstract

One major challenge in multiple sclerosis is to understand the cellular and molecular mechanisms leading to disease severity progression. The recently demonstrated correlation between disease severity and remyelination emphasizes the importance of identifying factors leading to a favourable outcome. Why remyelination fails or succeeds in multiple sclerosis patients remains largely unknown, mainly because remyelination has never been studied within a humanized pathological context that would recapitulate major events in plaque formation such as infiltration of inflammatory cells. Therefore, we developed a new paradigm by grafting healthy donor or multiple sclerosis patient lymphocytes in the demyelinated lesion of nude mice spinal cord. We show that lymphocytes play a major role in remyelination whose efficacy is significantly decreased in mice grafted with multiple sclerosis lymphocytes compared to those grafted with healthy donors lymphocytes. Mechanistically, we demonstrated in vitro that lymphocyte-derived mediators influenced differentiation of oligodendrocyte precursor cells through a crosstalk with microglial cells. Among mice grafted with lymphocytes from different patients, we observed diverse remyelination patterns reproducing for the first time the heterogeneity observed in multiple sclerosis patients. Comparing lymphocyte secretory profile from patients exhibiting high and low remyelination ability, we identified novel molecules involved in oligodendrocyte precursor cell differentiation and validated CCL19 as a target to improve remyelination. Specifically, exogenous CCL19 abolished oligodendrocyte precursor cell differentiation observed in patients with high remyelination pattern. Multiple sclerosis lymphocytes exhibit intrinsic capacities to coordinate myelin repair and further investigation on patients with high remyelination capacities will provide new pro-regenerative strategies.

LanguageEnglish (US)
Pages967-980
Number of pages14
JournalBrain : a journal of neurology
Volume140
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Demyelinating Diseases
Adaptive Immunity
Lymphocytes
Immunity
Mouse
Multiple Sclerosis
Cells
Oligodendroglia
Precursor
Cell Differentiation
Tissue Donors
Lymphokines
Myelin Sheath
Nude Mice
Disease Progression
Spinal Cord
In Vitro Techniques
Nude
Repair
Lesion

Keywords

  • lymphocytes
  • multiple sclerosis
  • neuroinflammation
  • remyelination

ASJC Scopus subject areas

  • Medicine(all)
  • Arts and Humanities (miscellaneous)
  • Clinical Neurology

Cite this

El Behi, M., Sanson, C., Bachelin, C., Guillot-Noël, L., Fransson, J., Stankoff, B., ... Zujovic, V. (2017). Adaptive human immunity drives remyelination in a mouse model of demyelination. Brain : a journal of neurology, 140(4), 967-980. DOI: 10.1093/brain/awx008

Adaptive human immunity drives remyelination in a mouse model of demyelination. / El Behi, Mohamed; Sanson, Charles; Bachelin, Corinne; Guillot-Noël, Léna; Fransson, Jennifer; Stankoff, Bruno; Maillart, Elisabeth; Sarrazin, Nadège; Guillemot, Vincent; Abdi, Hervé; Cournu-Rebeix, Isabelle; Fontaine, Bertrand; Zujovic, Violetta.

In: Brain : a journal of neurology, Vol. 140, No. 4, 01.04.2017, p. 967-980.

Research output: Research - peer-reviewArticle

El Behi, M, Sanson, C, Bachelin, C, Guillot-Noël, L, Fransson, J, Stankoff, B, Maillart, E, Sarrazin, N, Guillemot, V, Abdi, H, Cournu-Rebeix, I, Fontaine, B & Zujovic, V 2017, 'Adaptive human immunity drives remyelination in a mouse model of demyelination' Brain : a journal of neurology, vol 140, no. 4, pp. 967-980. DOI: 10.1093/brain/awx008
El Behi M, Sanson C, Bachelin C, Guillot-Noël L, Fransson J, Stankoff B et al. Adaptive human immunity drives remyelination in a mouse model of demyelination. Brain : a journal of neurology. 2017 Apr 1;140(4):967-980. Available from, DOI: 10.1093/brain/awx008
El Behi, Mohamed ; Sanson, Charles ; Bachelin, Corinne ; Guillot-Noël, Léna ; Fransson, Jennifer ; Stankoff, Bruno ; Maillart, Elisabeth ; Sarrazin, Nadège ; Guillemot, Vincent ; Abdi, Hervé ; Cournu-Rebeix, Isabelle ; Fontaine, Bertrand ; Zujovic, Violetta. / Adaptive human immunity drives remyelination in a mouse model of demyelination. In: Brain : a journal of neurology. 2017 ; Vol. 140, No. 4. pp. 967-980
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