Macrophages facilitate peripheral nerve regeneration by organizing regeneration tracks through Plexin-B2

Yuhuan Li, Sangjo Kang, Dalia Halawani, Yiqun Wang, Chrystian Junqueira Alves, Aarthi Ramakrishnan, Molly Estill, Li Shen, Fengtao Li, Xijing He, Roland H. Friedel, Hongyan Zou

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


The regeneration of peripheral nerves is guided by regeneration tracks formed through an interplay of many cell types, but the underlying signaling pathways remain unclear. Here, we demonstrate that macrophages are mobilized ahead of Schwann cells in the nerve bridge after transection injury to participate in building regeneration tracks. This requires the function of guidance receptor Plexin-B2, which is robustly up-regulated in infiltrating macrophages in injured nerves. Conditional deletion of Plexin-B2 in myeloid lineage resulted in not only macrophage misalignment but also matrix disarray and Schwann cell disorganization, leading to misguided axons and delayed functional recovery. Plexin-B2 is not required for macrophage recruitment or activation but enables macrophages to steer clear of colliding axons, in particular the growth cones at the tip of regenerating axons, leading to parallel alignment postcollision. Together, our studies unveil a novel reparative function of macrophages and the importance of Plexin-B2-mediated collision-dependent contact avoidance between macrophages and regenerating axons in forming regeneration tracks during peripheral nerve regeneration.

Original languageEnglish
Pages (from-to)133-148
Number of pages16
JournalGenes and Development
Issue number3-4
StatePublished - 1 Feb 2022


  • Axon regeneration
  • Collision guidance
  • Contact repulsion
  • Macrophages
  • Peripheral nerve injury
  • Plexin-B2]
  • Schwann cells


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