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Interleukin\u20103 (IL\u20103) has been implicated in programming microglia to cluster and clear pathological aggregates in neurodegenerative disease. Yet, the influence of IL\u20103 on lipid debris clearance post\u2010SCI is not well characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established a mouse model of spinal cord compression injury to investigate the role of IL\u20103. Blockage of IL\u20103 was achieved through intrathecal delivery of an IL\u20103\u2010neutralizing antibody, while IL\u20103 activation was augmented via in\u00a0situ injection of recombinant IL\u20103 into the lesion site immediately post\u2010SCI. Immunofluorescence staining was performed to determine IL\u20103 and IL\u20103R\u03b1 sources and distribution, lipid droplet accumulation, neuron preservation, and axon regeneration after SCI. The Basso Mouse Scale (BMS) and footprint analysis were employed to evaluate locomotor function recovery.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that IL\u20103 expression was significantly upregulated post\u2010SCI, peaking at 14\u2009days post\u2010injury (dpi) and persisting until 28\u2009dpi. Notably, IL\u20103 was primarily secreted by astrocytes surrounding the lesion epicenter. Correspondingly, IL\u20103R\u03b1 was predominantly observed in macrophages within the injury core, also elevating at 14\u2009dpi. Neutralization of IL\u20103 led to increased lipid droplet accumulation, along with markedly widespread of macrophages and decreased neuronal survival, resulting in severe motor deficits compared to controls. Conversely, in\u00a0situ injection of IL\u20103 reduced lipid droplet accumulation in macrophages, preserved neurons, promoted axon regeneration, and ultimately contributed to the recovery of motor function after SCI.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings shed light on the role of IL\u20103 in modulating macrophage phagocytic activity and suggest that the IL\u20103\/IL\u20103R\u03b1 pathway may be a potential therapeutic target for enhancing neural repair and functional recovery after SCI.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70181","type":"journal-article","created":{"date-parts":[[2024,12,19]],"date-time":"2024-12-19T09:40:56Z","timestamp":1734601256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interleukin\u20103 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair"],"prefix":"10.1111","volume":"30","author":[{"given":"Jianjian","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Institute of Orthopaedics, Research Center for Translational Medicine The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meige","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University  Hefei China"},{"name":"Institute of Orthopaedics, Research Center for Translational Medicine The Second Affiliated Hospital of Anhui Medical University  Hefei China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangru","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Orthopaedics The Second Affiliated Hospital of Anhui Medical University  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