PDF(Pubmed)
Abstract：
The immune system has garnered attention for its role in peripheral nerve regeneration, particularly as it pertains to regeneration across segmental injuries. Previous work demonstrated that eosinophils are recruited to regenerating nerve and express interleukin-4, amongst potential cytokines. These results suggest a direct role for eosinophils in promoting nerve regeneration. Therefore, we further considered eosinophils roles in nerve regeneration using a segmental nerve injury and Gata1 knockout (KO) mice, which are severely eosinophil deficient, compared to wild-type BALB/c mice (WT). Mice receiving a sciatic nerve gap injury demonstrated distinct cytokine expression and leukocytes within regenerating nerve. Compared to controls, Gata1 KO regenerated nerves contained decreased expression of type 2 cytokines, including Il-5 and Il-13, and decreased recruitment of eosinophils and macrophages. At this early time point during ongoing regeneration, the macrophages within Gata1 KO nerves also demonstrated significantly less M2 polarization compared to controls. Subsequently, motor and sensory axon regeneration across the gap injury was decreased in Gata1 KO compared to WT during ongoing nerve regeneration. Over longer observation to allow for more complete nerve regeneration, behavioral recovery measured by grid-walk assessment was not different comparing groups but modestly delayed in Gata1 KO compared to WT. The extent of final axon regeneration was not different amongst groups. Our data provide additional evidence suggesting eosinophils contribute to nerve regeneration across a nerve gap injury, but are not essential to regeneration in this context. Our evidence also suggests eosinophils may regulate cytokines that promote distinct macrophage phenotypes and axon regeneration.
摘要：
免疫系统在周围神经再生中的作用引起了人们的注意，特别是当它涉及到跨节段损伤的再生时。先前的工作表明，嗜酸性粒细胞被招募以再生神经并表达潜在的细胞因子中的白细胞介素4。这些结果表明嗜酸性粒细胞在促进神经再生中的直接作用。因此,我们进一步考虑了嗜酸性粒细胞在使用节段性神经损伤和Gata1敲除（KO）小鼠的神经再生中的作用，严重的嗜酸性粒细胞缺乏，与野生型BALB/c小鼠(WT)相比。接受坐骨神经间隙损伤的小鼠表现出不同的细胞因子表达和再生神经内的白细胞。与对照组相比，Gata1KO再生神经含有2型细胞因子表达降低，包括Il-5和Il-13,并且减少嗜酸性粒细胞和巨噬细胞的募集。在正在进行的再生过程中的这个早期时间点，与对照组相比，Gata1KO神经内的巨噬细胞也显示出明显更少的M2极化。随后，在正在进行的神经再生过程中，与WT相比，Gata1KO在间隙损伤中的运动和感觉轴突再生降低。经过更长时间的观察，以允许更完整的神经再生，与WT相比，Gata1KO通过网格行走评估测得的行为恢复与对照组相比没有差异，但略有延迟。最终轴突再生的程度在各组之间没有差异。我们的数据提供了额外的证据表明嗜酸性粒细胞有助于神经间隙损伤的神经再生，但在这种情况下对再生并不重要。我们的证据还表明嗜酸性粒细胞可能调节促进不同巨噬细胞表型和轴突再生的细胞因子。
