Blockade of Interleukin-7 Receptor Shapes Macrophage Alternative Activation and Promotes Functional Recovery After Spinal Cord Injury

Macrophages are implicated in the pathological processes and functional recovery of spinal cord injury (SCI). Macrophage activation following inflammation depends on networks of interferons and cytokines. Recent evidence indicate that IL-7 signaling can influence the release of proinflammatory factors, however, its roles in modulating macrophage phenotype and function and whether it could affect the functional recovery of SCI are poorly understood. Here, we show that, in a murine SCI model, IL-7 is promptly and vastly induced in injured spinal cord, and that blockade of IL-7 signaling with anti-IL-7R alpha mAb (A7R34) favors the generation of M2 phenotype macrophages by affecting the cytokine productions in T helper (Th) 1 and Th2 cells. Furthermore, IL-7 displays strong chemotactic property for macrophages and A7R34 treatment inhibits their infiltration into injured sites in vivo. More importantly, the A7R34 treatment promotes functional recovery after SCI, indicating its therapeutic effects on spinal cord repair. Hence, our study proposes a new therapeutic strategy to treat SCI by blocking IL-7 signaling. (C) 2017 IBRO. Published by Elsevier Ltd. All rights reserved.