Published in Nature Immunology. Bone marrow neutrophils polarized with IL-4 and G-CSF acquire alternative activation markers, produce growth factors, and drive substantial axon regeneration after CNS injury when adoptively transferred.
The adult central nervous system has a limited capacity for self-repair. Severed CNS axons typically fail to regrow, leaving an unmet need for treatments that enhance neuronal viability, facilitate axon regeneration, and restore lost neurological function in traumatic CNS injury, multiple sclerosis, stroke, and other neurological disorders.
This study shows that both mouse and human bone marrow neutrophils, polarized with a combination of recombinant interleukin-4 (IL-4) and granulocyte colony-stimulating factor (G-CSF), upregulate alternative activation markers and produce an array of growth factors, gaining the capacity to promote neurite outgrowth.
Adoptive transfer of IL-4/G-CSF-polarized bone marrow neutrophils into experimental models of CNS injury triggered substantial axon regeneration within the optic nerve and spinal cord. The findings have implications for autologous myeloid cell-based therapies aimed at reversing CNS damage.
The Quantitative Imaging Group contributed image analysis methods for the study.
Cytokine polarized, alternatively activated bone marrow neutrophils drive axon regeneration. Jerome AD, Sas AR, Wang Y, Hammond LA, Wen J, Atkinson JR, Webb A, Liu T, Segal BM. Nature Immunology. 2024;25(6):957-968.