Interleukin-3 Modulates Macrophage Phagocytic Activity and Promotes Spinal Cord Injury Repair.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101473265 Publication Model: Print Cited Medium: Internet ISSN: 1755-5949 (Electronic) Linking ISSN: 17555930 NLM ISO Abbreviation: CNS Neurosci Ther Subsets: MEDLINE

Original Publication: Oxford, UK : Wiley-Blackwell, c2008-

Spinal Cord Injuries*/pathology ; Spinal Cord Injuries*/metabolism ; Macrophages*/metabolism ; Macrophages*/drug effects ; Mice, Inbred C57BL* ; Interleukin-3*/metabolism; Animals ; Mice ; Female ; Phagocytosis/drug effects ; Phagocytosis/physiology ; Recovery of Function/physiology ; Recovery of Function/drug effects ; Disease Models, Animal

Background: Effective clearance of lipid-rich debris by macrophages is critical for neural repair and regeneration after spinal cord injury (SCI). Interleukin-3 (IL-3) has been implicated in programming microglia to cluster and clear pathological aggregates in neurodegenerative disease. Yet, the influence of IL-3 on lipid debris clearance post-SCI is not well characterized.
Methods: We established a mouse model of spinal cord compression injury to investigate the role of IL-3. Blockage of IL-3 was achieved through intrathecal delivery of an IL-3-neutralizing antibody, while IL-3 activation was augmented via in situ injection of recombinant IL-3 into the lesion site immediately post-SCI. Immunofluorescence staining was performed to determine IL-3 and IL-3Rα 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.
Results: We found that IL-3 expression was significantly upregulated post-SCI, peaking at 14 days post-injury (dpi) and persisting until 28 dpi. Notably, IL-3 was primarily secreted by astrocytes surrounding the lesion epicenter. Correspondingly, IL-3Rα was predominantly observed in macrophages within the injury core, also elevating at 14 dpi. Neutralization of IL-3 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 situ injection of IL-3 reduced lipid droplet accumulation in macrophages, preserved neurons, promoted axon regeneration, and ultimately contributed to the recovery of motor function after SCI.
Conclusion: Our findings shed light on the role of IL-3 in modulating macrophage phagocytic activity and suggest that the IL-3/IL-3Rα pathway may be a potential therapeutic target for enhancing neural repair and functional recovery after SCI.
(© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

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82271413 National Natural Science Foundation of China; 82372506 National Natural Science Foundation of China; 202304295107020009 Clinical Medical Research Transformation Project of Anhui Province; 202304295107020011 Clinical Medical Research Transformation Project of Anhui Province; 202304295107020013 Clinical Medical Research Transformation Project of Anhui Province; 202304295107020014 Clinical Medical Research Transformation Project of Anhui Province; 2208085MH222 Anhui Provincial Natural Science Foundation; 2308085MH257 Anhui Provincial Natural Science Foundation; 2022AH050650 Natural Science Research Project of Anhui Educational Committee; 2022AH050713 Natural Science Research Project of Anhui Educational Committee; 2022AH050746 Natural Science Research Project of Anhui Educational Committee; KJ2021A0310 Natural Science Research Project of Anhui Educational Committee; GZC20230027 Postdoctoral Fellowship Program of CPSF

Keywords: IL‐3; IL‐3Rα; SCI; astrocyte; lipid droplets; macrophage

0 (Interleukin-3)

Date Created: 20241219 Date Completed: 20241219 Latest Revision: 20250730

20250731

PMC11656101

10.1111/cns.70181

39697159