MMP2 Modulates Inflammatory Response during Axonal Regeneration in the Murine Visual System

• Published in: Cells (Basel, Switzerland) Switzerland), 2021-07, Vol.10 (7), p.1672
• Main Authors: Andries, Lien, Masin, Luca, Salinas-Navarro, Manuel, Zaunz, Samantha, Claes, Marie, Bergmans, Steven, Brouwers, Véronique, Lefevere, Evy, Verfaillie, Catherine, Movahedi, Kiavash, De Groef, Lies, Moons, Lieve
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Ly - genetics; Antigens, Ly - immunology; axonal regeneration; Axons; Axons - immunology; Axons - ultrastructure; Bone marrow; Bone Marrow Transplantation; Cell Movement; Central nervous system; CX3C Chemokine Receptor 1 - genetics; CX3C Chemokine Receptor 1 - immunology; Development and progression; Experiments; expression profiling; GAP-43 Protein - genetics; GAP-43 Protein - immunology; Gelatinase A; Gene Expression Regulation; Health aspects; Immunity, Innate; Inflammation; inflammatory stimulation; Leukocyte Common Antigens - genetics; Leukocyte Common Antigens - immunology; Mammals; Matrix Metalloproteinase 2 - deficiency; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 2 - immunology; matrix metalloproteinases; Metalloenzymes; Mice; Mice, Inbred C57BL; Mice, Knockout; Myeloid cells; Myeloid Cells - cytology; Myeloid Cells - immunology; Nerve Regeneration - genetics; Nerve Regeneration - immunology; Nervous system; Neurological research; Optic nerve; Optic Nerve - immunology; Optic Nerve - metabolism; Optic Nerve Injuries - genetics; Optic Nerve Injuries - immunology; Optic Nerve Injuries - pathology; optic nerve injury; Phenotypes; Regeneration; Retina - immunology; Retina - injuries; Retina - metabolism; Scars; Spinal cord; Stem cell transplantation; Transplantation, Heterologous; Visual system; Whole-Body Irradiation
• ISSN: 2073-4409; 2073-4409
• DOI: 10.3390/cells10071672

Neuroinflammation has been put forward as a mechanism triggering axonal regrowth in the mammalian central nervous system (CNS), yet little is known about the underlying cellular and molecular players connecting these two processes. In this study, we provide evidence that MMP2 is an essential factor linking inflammation to axonal regeneration by using an in vivo mouse model of inflammation-induced axonal regeneration in the optic nerve. We show that infiltrating myeloid cells abundantly express MMP2 and that MMP2 deficiency results in reduced long-distance axonal regeneration. However, this phenotype can be rescued by restoring MMP2 expression in myeloid cells via a heterologous bone marrow transplantation. Furthermore, while MMP2 deficiency does not affect the number of infiltrating myeloid cells, it does determine the coordinated expression of pro- and anti-inflammatory molecules. Altogether, in addition to its role in axonal regeneration via resolution of the glial scar, here, we reveal a new mechanism via which MMP2 facilitates axonal regeneration, namely orchestrating the expression of pro- and anti-inflammatory molecules by infiltrating innate immune cells.