title: C-C motif chemokine ligand 20 regulates neuroinflammation following spinal cord injury via Th17 cell recruitment.
abstract: Spinal cord injury (SCI) is a severe traumatic injury that often leads to paralysis. The neuroinflammation following SCI plays an important role during the secondary injury phase. C-C motif chemokine ligand 20 (CCL20) works like a magnet to attract inflammatory cells and subsequently regulate inflammation. However, the role and mechanisms of CCL20 in neuroinflammation following traumatic injury are poorly understood.
  
  
  
  A modified Allen's weight drop method was applied to induce a rat moderate contusion injury model. HE staining was used to assess spinal cord histopathology, and the water content test was used to estimate spinal cord edema. Motor function scores were quantified to evaluate locomotor ability, and leukocyte infiltration was observed by CD45 immunofluorescence and flow cytometry. Additionally, qRT-PCR and ELISA were used to determine inflammatory mediator gene expression. Th17 cell recruitment was identified by flow cytometry.
  
  
  
  Compared with the injury control groups, histological analysis of the lesion area and tissue edema revealed reduced spinal cord edema and decreased lesion volume in the group administrated with CCL20 neutralizing antibody. Locomotor activity, as assessed by Basso, Beattie, and Bresnahan (BBB) score, showed that CCL20 blockade was beneficial for motor function recovery. Results also showed that leukocyte infiltration was reduced by neutralizing CCL20 at 7 days post-injury. More importantly, expression levels of IL-1β, IL-6, and TNF-α at 24 h after SCI demonstrated that a reduced inflammatory reaction in the CCL20 antibody group compared with the injury controls. Although CCL20 altered the expression of IL-1β, IL-6, and TNF-α, it had no effect on anti-inflammatory IL-10 expression at 24 h after damage. Notably, tissue flow cytometry confirmed that Th17 cell recruitment in the CCL20 antibody group was decreased compared with the control groups at 14 days post-injury. Additionally, IL-17A expression, which is mainly secreted by Th17 cell, suggested that CCL20 blockade also reduced IL-17A levels at 14 days after SCI.
  
  
  
  These results suggested that CCL20 aggravates neuroinflammation following SCI via regulation of Th17 cell recruitment and IL-17A level. Thus, CCL20-target therapy could be a promising clinical application for the treatment of SCI.
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, People's Republic of China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Spine Surgery, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, People's Republic of China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, People's Republic of China.
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Sports Medicine, Research Center of Sports Medicine, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410000, People's Republic of China. hongbinlu@hotmail.com.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Lu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D054418:Chemokine CCL20 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology; D005434:Flow Cytometry; D007249:Inflammation / Q000188:drug therapy* / Q000209:etiology*; D020381:Interleukin-17 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008024:Ligands; D008124:Locomotion / Q000187:drug effects; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000150:complications*; D058504:Th17 Cells / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D000911:Antibodies, Monoclonal; D054418:Chemokine CCL20; D020381:Interleukin-17; D008024:Ligands; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens
keywords: CCL20; Chemokine; Flow cytometry; Neuroinflammation; Spinal cord injury; Th17