Neuroectodermal interleukin 12 signaling attenuates spinal cord inflammation and demyelination

INTRODUCTION: Interleukin 12 (IL-12) is a driver of type 1 immunity. Interleukin 12 reduces inflammation in an autoimmune condition in the spinal cord. The aim of this study was to investigate the therapeutic effect of IL-12 in the experimental autoimmune encephalomyelitis model. MATERIAL AND METHODS: Interleukin 12 expression was mapped in neurons, oligodendrocytes, natural killer cells, and T lymphocyte cells in the spinal cord of experimental autoimmune encephalomyelitis mice. RESULTS: Interleukin 12 ablation in neurons, oligodendrocytes, natural killer, and T lymphocyte cells in mice and their susceptibility to experimental autoimmune encephalomyelitis showed that the neuroprotective role of IL-12 is mediated by neuroectoderm-derived cells - neurons. CONCLUSIONS: Single-nucleus RNA sequencing revealed an IL-12 receptor-induced neuroprotective effect that prevents neurodegeneration, sustains trophic factor release in neuroinflammation, and maintains spinal cord integrity.