Research Paper Volume 11, Issue 18 pp 7402—7415

CCL28 promotes locomotor recovery after spinal cord injury via recruiting regulatory T cells

Pengfei Wang1, , Xiangbei Qi2, , Guohui Xu2, , Jianning Liu2, , Jichao Guo2, , Xu Li2, , Xinzhe Ma2, , Hui Sun2, ,

  • 1 Department of Neurosurgery, The Third Hospital, Hebei Medical University, Shijiazhuang 050051, China
  • 2 Department of Orthopaedics, The Third Hospital, Hebei Medical University, Shijiazhuang 050051, China

Received: February 21, 2019       Accepted: August 22, 2019       Published: September 26, 2019
How to Cite

Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Background: Chemokines play a key role in post-traumatic inflammation and secondary injury after spinal cord injury (SCI). CCL28, the chemokine CC-chemokine ligand 28, is involved in the epithelial and mucosal immunity. However, whether CCL28 participates in the physiopathologic processes after SCI remains unclear.

Results: CCL28 is upregulated in the spinal cord after SCI. In addition, neutralizing antibodies against IL-1β or TNF-α, or treatment of ML120B, a selective inhibitor of IKK-β, remarkably decrease CCL28 upregulation, suggesting that CCL28 upregulation relies on NF-κB pathway activated by IL-1β and TNF-α after SCI. Moreover, CD4+CD25+FOXP3+ regulatory T (Treg) cells that express CCR10, a receptor of CCL28, are enriched in the spinal cord after SCI. We further demonstrate that the spinal cord recruits Treg cells through CCL28-CCR10 axis, which in turn function to suppress immune response and promote locomotor recovery after SCI. In contrast, neutralizing CCL28 or CCR10 reduces Treg cell recruitment and delays locomotor recovery.

Methods: The neutralizing antibodies and recombinant CCL28 were injected intraspinally into the mice prior to SCI, which was established via hemitransection. RT-qPCR analysis was performed to determine transcript level, and Western blot analysis and ELISA assay were used to detect protein expression. Immune cells were analyzed by flow cytometry and visualized by immunofluorescence. The chemotaxis was assessed by in vitro transwell migration assay. The mouse locomotor activity was assessed via the Basso Mouse Scale (BMS) system.

Conclusions: These results indicate that NF-κB pathway-regulated CCL28 production plays a protective role after SCI through recruiting CCR10-expressing and immunosuppressive Treg cells, and suggest that interfering CCL28-CCR10 axis might be of potential clinical benefit in improving SCI recovery.


SCI: spinal cord injury; Treg: regulatory T; BSB: blood-spinal cord barrier; MEC: mucosae-associated epithelial chemokine; ANOVA: analyzed by repeated measures analysis of variance; rMCCL28: recombinant CCL28; PBMCs: peripheral blood mononuclear cells; BMS: Basso Mouse Scale.