eprintid: 10205450 rev_number: 7 eprint_status: archive userid: 699 dir: disk0/10/20/54/50 datestamp: 2025-02-28 11:48:29 lastmod: 2025-02-28 11:48:29 status_changed: 2025-02-28 11:48:29 type: article metadata_visibility: show sword_depositor: 699 creators_name: Van Emmenis, L creators_name: Mòdol-Caballero, G creators_name: Harford-Wright, E creators_name: Power, A creators_name: Cattin, AL creators_name: White, IJ creators_name: Casal, G creators_name: Boal-Carvalho, I creators_name: Bennett, CL creators_name: Lloyd, AC title: Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: C10 divisions: D19 divisions: G98 divisions: D77 keywords: CCL3, CP: Cell biology, CP: Neuroscience, Schwann cells, chemotaxis, macrophages, migration, nerve injury, neuromas, pain, peripheral nerves, regeneration note: Copyright © 2025 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). abstract: 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. date: 2025-02-25 date_type: published publisher: Elsevier BV official_url: https://doi.org/10.1016/j.celrep.2025.115322 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green verified: verified_manual elements_id: 2363085 doi: 10.1016/j.celrep.2025.115322 medium: Print-Electronic pii: S2211-1247(25)00093-2 lyricists_name: Lloyd, Alison lyricists_name: Bennett, Clare lyricists_name: Casal, Giulia lyricists_id: ACLLO84 lyricists_id: CBENN26 lyricists_id: GCASA44 actors_name: Lloyd, Alison actors_id: ACLLO84 actors_role: owner full_text_status: public publication: Cell Reports volume: 44 number: 2 article_number: 115322 event_location: United States issn: 2639-1856 citation: Van Emmenis, L; Mòdol-Caballero, G; Harford-Wright, E; Power, A; Cattin, AL; White, IJ; Casal, G; ... Lloyd, AC; + view all <#> Van Emmenis, L; Mòdol-Caballero, G; Harford-Wright, E; Power, A; Cattin, AL; White, IJ; Casal, G; Boal-Carvalho, I; Bennett, CL; Lloyd, AC; - view fewer <#> (2025) Identification of CCL3 as a Schwann cell chemotactic factor essential for nerve regeneration. Cell Reports , 44 (2) , Article 115322. 10.1016/j.celrep.2025.115322 <https://doi.org/10.1016/j.celrep.2025.115322>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10205450/1/Van%20Emmenis%20el%20al%20published%20PDF.pdf