Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury

Journal of Neuroinflammation

Min-min Chang¹  Cheng Zhong²  Hao-Ran Zhu³  Guo-Dong Sun³  Ping Xu³  Wen-Cai Zhang³  Zhi-Zhong Li⁴  Si-Tao Li⁵  Feng Zhang⁶  Jing-Chun Yao⁷  Cheng-Hong Sun⁷ 

[1] College of Traditional Chinese Medicine, Jinan University, Guangzhou, China;Department of Orthopedics, The Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan University, Jiangmen, China;Department of Orthopedics, The First Affiliated Hospital of Jinan University, 601 West Whampoa Avenue, 510000, Guangzhou, China;Department of Orthopedics, The First Affiliated Hospital of Jinan University, 601 West Whampoa Avenue, 510000, Guangzhou, China;Heyuan Affiliated Hospital of Jinan University, 733 Wenxiang Road, 517000, Heyuan, China;Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Erheng Road, Tianhe District, 510655, Guangzhou, China;Intensive Care Unit, First Affiliated Hospital, Jinan University, Guangzhou, China;State Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. Ltd., Linyi, China;

关键词: Spinal cord injury;    Inflammation;    γδ T cell;    CCL2;    CCR2;   

DOI  :  10.1186/s12974-021-02115-0

来源: Springer

【 摘 要 】

BackgroundImmune cell infiltration and neuroinflammation are heavily associated with spinal cord injury (SCI). C-C motif chemokine ligand 2/C-C chemokine receptor type 2 (CCL2/CCR2) axis has been identified as a critical role player during the invasion of immune cells to lesions in many diseases. γδ T cells, a subgroup of T cells, manage the course of inflammation response in various diseases; however, it remains unknown whether γδ T cells are recruited to injury site through CCL2/CCR2 signaling and exert the regulation effect on neuroinflammation after SCI.MethodsBasso Mouse Scale (BMS), regularity index, cadence, max contact area, and motor-evoked potential testing (MEP) were measured to determine the neurological function recovery after spinal cord injury. Nissl staining was performed to identify the number of surviving motor neurons at lesion epicenter. Immunofluorescence, Western blot, enzyme-linked immunosorbent assays (ELISA), and quantitative real-time polymerase chain reaction (QRT-PCR) also were employed to evaluate the expression of associated proteins and genes.ResultsIn this study, we demonstrated that TCRδ−/− mice present improved neurological recovery after SCI. γδ T cell recruitment to the SCI site was significantly reduced and motor functional improvement enhanced in CCL2−/− and CCR2−/− mouse strains. Furthermore, reconstitution of TCRδ−/− mice with γδ T cells extracted from CCR2−/− mice also showed similar results to CCL2 and CCR2 deficient mice.ConclusionsIn conclusion, γδ T cell recruitment to SCI site promotes inflammatory response and exacerbates neurological impairment. CCL2/CCR2 signaling is a vital recruitment mechanism of γδ T cells to the SCI site, and it may be taken as a novel therapeutic target for future SCI.

【 授权许可】

CC BY