Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration
Summary: Peripheral nerves regenerate following injury, in contrast to those of the central nervous system. This involves the collective migration of Schwann cell (SC) cords, which transport regrowing axons across the wound site. The SC cords migrate along a newly formed vasculature, which bridges t...
| Published in: | Cell Reports |
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| Main Authors: | , , , , , , , , , |
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
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| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725000932 |
| _version_ | 1849530311786889216 |
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| author | Lucie Van Emmenis Guillem Mòdol-Caballero Elizabeth Harford-Wright Alex Power Anne-Laure Cattin Ian J. White Giulia Casal Inês Boal-Carvalho Clare L. Bennett Alison C. Lloyd |
| author_facet | Lucie Van Emmenis Guillem Mòdol-Caballero Elizabeth Harford-Wright Alex Power Anne-Laure Cattin Ian J. White Giulia Casal Inês Boal-Carvalho Clare L. Bennett Alison C. Lloyd |
| author_sort | Lucie Van Emmenis |
| collection | DOAJ |
| container_title | Cell Reports |
| description | Summary: Peripheral nerves regenerate following injury, in contrast to those of the central nervous system. This involves the collective migration of Schwann cell (SC) cords, which transport regrowing axons across the wound site. The SC cords migrate along a newly formed vasculature, which bridges the wound site in response to vascular endothelial growth factor, secreted by hypoxic macrophages. However, the directional signals by which SC cords navigate the long distances across the wound, in the absence of those that guide axons during development, remain unknown. Here, we identify CCL3 as the SC chemotactic factor, secreted by hypoxic macrophages, responsible for this process. We show that CCL3 promotes collective SC migration and axonal regrowth in vivo and, using genetic mouse models and widely used CCL3 inhibitors, that CCL3 is essential for effective nerve regeneration. These findings have therapeutic implications for both promoting nerve repair and inhibiting the aberrant nerve growth associated with trauma and disease. |
| format | Article |
| id | doaj-art-e51b47d61dcf48eca4b9dbb78dae4120 |
| institution | Directory of Open Access Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| spelling | doaj-art-e51b47d61dcf48eca4b9dbb78dae41202025-08-20T02:48:23ZengElsevierCell Reports2211-12472025-02-0144211532210.1016/j.celrep.2025.115322Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regenerationLucie Van Emmenis0Guillem Mòdol-Caballero1Elizabeth Harford-Wright2Alex Power3Anne-Laure Cattin4Ian J. White5Giulia Casal6Inês Boal-Carvalho7Clare L. Bennett8Alison C. Lloyd9UCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UKDepartment of Haematology, UCL Cancer Institute, University College London, London WC1E 6DD, UKDepartment of Haematology, UCL Cancer Institute, University College London, London WC1E 6DD, UKUCL Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK; Corresponding authorSummary: Peripheral nerves regenerate following injury, in contrast to those of the central nervous system. This involves the collective migration of Schwann cell (SC) cords, which transport regrowing axons across the wound site. The SC cords migrate along a newly formed vasculature, which bridges the wound site in response to vascular endothelial growth factor, secreted by hypoxic macrophages. However, the directional signals by which SC cords navigate the long distances across the wound, in the absence of those that guide axons during development, remain unknown. Here, we identify CCL3 as the SC chemotactic factor, secreted by hypoxic macrophages, responsible for this process. We show that CCL3 promotes collective SC migration and axonal regrowth in vivo and, using genetic mouse models and widely used CCL3 inhibitors, that CCL3 is essential for effective nerve regeneration. These findings have therapeutic implications for both promoting nerve repair and inhibiting the aberrant nerve growth associated with trauma and disease.http://www.sciencedirect.com/science/article/pii/S2211124725000932CP: NeuroscienceCP: Cell biology |
| spellingShingle | Lucie Van Emmenis Guillem Mòdol-Caballero Elizabeth Harford-Wright Alex Power Anne-Laure Cattin Ian J. White Giulia Casal Inês Boal-Carvalho Clare L. Bennett Alison C. Lloyd Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration CP: Neuroscience CP: Cell biology |
| title | Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration |
| title_full | Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration |
| title_fullStr | Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration |
| title_full_unstemmed | Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration |
| title_short | Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration |
| title_sort | identification of ccl3 as a schwann cell chemotactic factor essential for nerve regeneration |
| topic | CP: Neuroscience CP: Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725000932 |
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