Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury
Abstract Background Immune 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 di...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-03-01
|
| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-021-02115-0 |
| _version_ | 1818615400247590912 |
|---|---|
| author | Ping Xu Feng Zhang Min-min Chang Cheng Zhong Cheng-Hong Sun Hao-Ran Zhu Jing-Chun Yao Zhi-Zhong Li Si-Tao Li Wen-Cai Zhang Guo-Dong Sun |
| author_facet | Ping Xu Feng Zhang Min-min Chang Cheng Zhong Cheng-Hong Sun Hao-Ran Zhu Jing-Chun Yao Zhi-Zhong Li Si-Tao Li Wen-Cai Zhang Guo-Dong Sun |
| author_sort | Ping Xu |
| collection | DOAJ |
| description | Abstract Background Immune 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. Methods Basso 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. Results In 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. Conclusions In 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. |
| first_indexed | 2024-12-16T16:33:18Z |
| format | Article |
| id | doaj.art-88cc0d6c5bd24d5ebea7ee7eb446927c |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-12-16T16:33:18Z |
| publishDate | 2021-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-88cc0d6c5bd24d5ebea7ee7eb446927c2022-12-21T22:24:31ZengBMCJournal of Neuroinflammation1742-20942021-03-0118111610.1186/s12974-021-02115-0Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injuryPing Xu0Feng Zhang1Min-min Chang2Cheng Zhong3Cheng-Hong Sun4Hao-Ran Zhu5Jing-Chun Yao6Zhi-Zhong Li7Si-Tao Li8Wen-Cai Zhang9Guo-Dong Sun10Department of Orthopedics, The First Affiliated Hospital of Jinan UniversityIntensive Care Unit, First Affiliated Hospital, Jinan UniversityCollege of Traditional Chinese Medicine, Jinan UniversityDepartment of Orthopedics, The Affiliated Jiangmen Traditional Chinese Medicine Hospital of Jinan UniversityState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. Ltd.Department of Orthopedics, The First Affiliated Hospital of Jinan UniversityState Key Laboratory of Generic Manufacture Technology of Chinese Traditional Medicine, Lunan Pharmaceutical Group Co. Ltd.Department of Orthopedics, The First Affiliated Hospital of Jinan UniversityDepartment of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen UniversityDepartment of Orthopedics, The First Affiliated Hospital of Jinan UniversityDepartment of Orthopedics, The First Affiliated Hospital of Jinan UniversityAbstract Background Immune 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. Methods Basso 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. Results In 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. Conclusions In 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.https://doi.org/10.1186/s12974-021-02115-0Spinal cord injuryInflammationγδ T cellCCL2CCR2 |
| spellingShingle | Ping Xu Feng Zhang Min-min Chang Cheng Zhong Cheng-Hong Sun Hao-Ran Zhu Jing-Chun Yao Zhi-Zhong Li Si-Tao Li Wen-Cai Zhang Guo-Dong Sun Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury Journal of Neuroinflammation Spinal cord injury Inflammation γδ T cell CCL2 CCR2 |
| title | Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
| title_full | Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
| title_fullStr | Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
| title_full_unstemmed | Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
| title_short | Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
| title_sort | recruitment of γδ t cells to the lesion via the ccl2 ccr2 signaling after spinal cord injury |
| topic | Spinal cord injury Inflammation γδ T cell CCL2 CCR2 |
| url | https://doi.org/10.1186/s12974-021-02115-0 |
| work_keys_str_mv | AT pingxu recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT fengzhang recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT minminchang recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT chengzhong recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT chenghongsun recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT haoranzhu recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT jingchunyao recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT zhizhongli recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT sitaoli recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT wencaizhang recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury AT guodongsun recruitmentofgdtcellstothelesionviatheccl2ccr2signalingafterspinalcordinjury |