Macrophage‑based delivery of interleukin‑13 improves functional and histopathological outcomes following spinal cord injury

Journal of Neuroinflammation, 2022 · DOI: https://doi.org/10.1186/s12974-022-02458-2 · Published: April 7, 2022

Simple Explanation

Spinal cord injury (SCI) triggers inflammation that worsens the initial damage. Macrophages and microglia play a key role in this inflammatory response. This study explores using macrophages to deliver interleukin-13 (IL-13), an anti-inflammatory substance, directly to the injury site to promote healing. Macrophages were genetically modified to secrete IL-13 (IL-13 Mφs) and injected into mice with SCI. The study assessed functional recovery and tissue repair. The results showed that delivering IL-13 using macrophages improved recovery after spinal cord injury in mice. The improvement was linked to reduced tissue damage and a decrease in inflammation. The researchers also discovered that IL-13 signaling is essential for these benefits. The findings suggest that IL-13 and modulation of macrophage/microglia can potentially aid in regeneration following CNS trauma.

Study Duration

4 Weeks

Participants

Female mice (WT BALB/c, C57BL/6J, CX3CR1+/GFP, IL-4Rα control and knockout)

Evidence Level

Not specified

Key Findings

1
Transplantation of IL-13 Mφs promoted functional recovery following SCI in mice, indicated by significantly improved Basso Mouse Scale (BMS) scores compared to vehicle and M2 Mφ groups.
2
Histological analyses revealed that mice treated with IL-13 Mφs exhibited significantly reduced lesion size and a trend toward decreased demyelination compared to the vehicle control group.
3
IL-13 Mφ treatment increased the amount of Arg1+ cells at the lesion site while reducing the number of MHCII+ cells compared to vehicle, indicating an anti-inflammatory shift in perilesional phagocytes.

Research Summary

This study investigates the therapeutic potential of macrophage-based delivery of interleukin-13 (IL-13) to improve functional and histopathological outcomes following spinal cord injury (SCI) in mice. The results demonstrate that perilesional transplantation of IL-13-secreting macrophages (IL-13 Mφs) promoted functional recovery, reduced lesion size and demyelination, and induced an anti-inflammatory shift in phagocytes at the lesion site. Further experiments using IL-4Rα-deficient mice and Arg1-overexpressing macrophages confirmed that IL-13 signaling is critical for the observed neuroprotective and functional benefits, highlighting the potential of IL-13 as an immunomodulatory therapy for SCI.

Practical Implications

Therapeutic Strategy

IL-13 delivery by genetically modified macrophages is a promising therapeutic approach for improving functional recovery after SCI.

Immunomodulatory Target

IL-13 is a prime candidate for effective immunomodulation after SCI to improve repair, suggesting potential clinical applications.

Neuroprotection Mechanism

IL-13 elicits neuroprotection indirectly by stimulating anti-inflammatory responses in macrophages/microglia and ameliorating axonal dieback, facilitating regeneration.

Study Limitations

1
Only female mice were used, which may limit the generalizability of the results due to sex differences in SCI outcomes and inflammatory responses.
2
The exact mechanisms underlying the reduction in foamy cells and the role of IL-13 in phagocytosis require further investigation.
3
The inability to trace IL-13 Mφs beyond 8 days post-SCI limits understanding of the long-term effects and cell persistence requirements for functional recovery.

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