Loading

Commentary Open Access
Volume 3 | Issue 1 | DOI: https://doi.org/10.46439/signaling.3.077

Neuroimmune interplay in peripheral neuropathies

  • 1National Center for Orthopaedics, Department of Orthopaedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China
  • 2Department of Immunology, the School of Cell and Gene Therapy, Shanghai Jiao Tong University School of Medicine; Shanghai, 201600, China
+ Affiliations - Affiliations

Corresponding Author

Cunyi Fan, cyfan@sjtu.edu.cn;
Song Guo Zheng, Song.Zheng@shsmu.edu.cn

Received Date: July 28, 2025

Accepted Date: September 05, 2025

Abstract

The interplay between neural cells and immune cells is a determinant factor for microenvironment restoration following nerve injury. Nerve-resident immune cells respond microenvironment signals and switch to pro-inflammatory or pro-regenerative phenotype. These phenotypes have different effects on axon regeneration. Early-phase neuroinflammation clears debris and remodels a permissive microenvironment for nerve repair. However, persistent and overactive inflammation is destructive and detrimental to regeneration. Despite all this information, our understanding of neuroimmune interplay in traumatic and diabetic neuropathies remains poor. Early studies on neuroimmune interplay focused on tissue defenses, in which nerve ending modulates the immune function in peripheral tissues, maximizing the sensing and defensing abilities to environmental aggressions. With the identification of cellular and molecular profile of injured nerves, the interaction between immune cells and other nerve-resident cells, e.g., Schwann cells and vessel cells, becomes clearer. In our recently published studies, we identified key proteins that impacts the regeneration of injured nerves by proteomic sequencing. We also identified that mast cells play key roles in DPN progression by single-cell RNA sequencing. These discoveries were further verified in transgenic mice. This commentary summarizes the neuroimmune interplay in diabetic peripheral neuropathy and traumatic peripheral nerve injury, and the potential treatment via blockade of neuroimmune axis.

Keywords

Neuroimmune interplay, Diabetes, Trauma, Neuropathy, Neuroinflammation

Author Information X