The inflammatory APRIL (a proliferation-inducing ligand) antagonizes chondroitin sulphate proteoglycans to promote axonal growth and myelination
Lesions in the CNS are frequently associated to a detrimental inflammatory reaction. In autoimmune neurodegenerative diseases, a proliferation-inducing ligand (APRIL) produced by CNS-infiltrating inflammatory cells binds to chondroitin sulphate proteoglycans (CSPGs). The latter are well-established obstacles to neural regeneration and remyelination in the CNS by interacting with receptor protein tyrosine phosphatase (RPTP) and Nogo receptor (NgR) families. Here, we are showing that APRIL blocks the interactions of RPTP and NgR with all types of chondroitin sulphate (CS). Functionally, APRIL neutralized the inhibitory effects of CS on mouse and human neuronal process growth. APRIL also blocked the inhibition of CS on mouse and human oligodendrocyte differentiation. Finally, APRIL increased myelination in an <i>ex vivo</i> organotypic model of demyelination in the presence of endogenous CSPG upregulation. Our data demonstrate the potential value for a recombinant form of soluble APRIL to achieve repair in the CNS.
Authors
- Bertrand Huard (ORCID: https://orcid.org/0000-0003-1358-6576)
- Una FitzGerald (ORCID: https://orcid.org/0000-0002-8019-6546)
- Mehrnaz Jafarian-Tehrani (ORCID: https://orcid.org/0000-0001-6895-5856)
- Delphine Meffre (ORCID: https://orcid.org/0000-0002-9204-2245)
- Romain R. Vivès (ORCID: https://orcid.org/0000-0003-4295-5449)
- Laureen Grewing
- Pascal Schneider (ORCID: https://orcid.org/0000-0003-0677-9409)
- Tanja Kuhlmann (ORCID: https://orcid.org/0000-0002-0174-5042)
- Leticia Peris (ORCID: https://orcid.org/0000-0002-0668-1252)
- Elif Nur Yılmaz (ORCID: https://orcid.org/0000-0003-0363-0895)
- Evelyne Gout (ORCID: https://orcid.org/0000-0002-5424-6474)
- Benoît Manfroi (ORCID: https://orcid.org/0000-0002-4105-4684)
- Mashal Claude Ahmed
- Raquel Guerrero González (ORCID: https://orcid.org/0009-0007-9235-770X)
- Tejaswini Kakunuri
Institutions
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Ollscoil na Gaillimhe – University of Galway (IE)
- Université Paris Cité (FR)
- Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR)
- CEA Grenoble (FR)
- Sorbonne Paris Cité (FR)
- University Hospital Münster (DE)
- Grenoble Institute of Neurosciences (FR)
- Institut de Biologie Structurale (FR)
- Université Grenoble Alpes (FR)
- University of Lausanne (CH)
Publication Details
- Journal
- Brain Communications
- Published
- 2024-12-24
- DOI
- https://doi.org/10.1093/braincomms/fcae473
- Citations
- 1
- Primary Topic
- Proteoglycans and glycosaminoglycans research
- Type
- article
- Field-Weighted Citation Impact
- 0.33
Funders
- European Commission
- Agence Nationale de la Recherche
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung