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Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury
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....
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927238/ https://www.ncbi.nlm.nih.gov/pubmed/33653377 http://dx.doi.org/10.1186/s12974-021-02115-0 |
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author | Xu, Ping Zhang, Feng Chang, Min-min Zhong, Cheng Sun, Cheng-Hong Zhu, Hao-Ran Yao, Jing-Chun Li, Zhi-Zhong Li, Si-Tao Zhang, Wen-Cai Sun, Guo-Dong |
author_facet | Xu, Ping Zhang, Feng Chang, Min-min Zhong, Cheng Sun, Cheng-Hong Zhu, Hao-Ran Yao, Jing-Chun Li, Zhi-Zhong Li, Si-Tao Zhang, Wen-Cai Sun, Guo-Dong |
author_sort | Xu, Ping |
collection | PubMed |
description | 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02115-0. |
format | Online Article Text |
id | pubmed-7927238 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-79272382021-03-03 Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury Xu, Ping Zhang, Feng Chang, Min-min Zhong, Cheng Sun, Cheng-Hong Zhu, Hao-Ran Yao, Jing-Chun Li, Zhi-Zhong Li, Si-Tao Zhang, Wen-Cai Sun, Guo-Dong J Neuroinflammation Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12974-021-02115-0. BioMed Central 2021-03-02 /pmc/articles/PMC7927238/ /pubmed/33653377 http://dx.doi.org/10.1186/s12974-021-02115-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Xu, Ping Zhang, Feng Chang, Min-min Zhong, Cheng Sun, Cheng-Hong Zhu, Hao-Ran Yao, Jing-Chun Li, Zhi-Zhong Li, Si-Tao Zhang, Wen-Cai Sun, Guo-Dong Recruitment of γδ T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury |
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 | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927238/ https://www.ncbi.nlm.nih.gov/pubmed/33653377 http://dx.doi.org/10.1186/s12974-021-02115-0 |
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