Temporal dynamics of neutrophil functions in multiple sclerosis

Early neuroinflammatory injury plays a crucial role in initiating and progressing multiple sclerosis (MS). Neutrophils are forerunners to neural lesions in MS, yet the temporal alterations of their functions in MS remains unclear. This study demonstrated a positive correlation between circulatory ne...

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Main Authors: Shishi Shen, Shilin Wu, Yuge Wang, Li Xiao, Xiaobo Sun, Wenxuan Sun, Yipeng Zhao, Rui Li, Jiaqi Zhang, Zhanhang Wang, Shaoli Zhou, Shixiong Huang, Yanyu Chang, Yaqing Shu, Chen Chen, Zhengqi Lu, Wei Cai, Wei Qiu
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Neurobiology of Disease
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Online Access:http://www.sciencedirect.com/science/article/pii/S0969996124003462
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author Shishi Shen
Shilin Wu
Yuge Wang
Li Xiao
Xiaobo Sun
Wenxuan Sun
Yipeng Zhao
Rui Li
Jiaqi Zhang
Zhanhang Wang
Shaoli Zhou
Shixiong Huang
Yanyu Chang
Yaqing Shu
Chen Chen
Zhengqi Lu
Wei Cai
Wei Qiu
author_facet Shishi Shen
Shilin Wu
Yuge Wang
Li Xiao
Xiaobo Sun
Wenxuan Sun
Yipeng Zhao
Rui Li
Jiaqi Zhang
Zhanhang Wang
Shaoli Zhou
Shixiong Huang
Yanyu Chang
Yaqing Shu
Chen Chen
Zhengqi Lu
Wei Cai
Wei Qiu
author_sort Shishi Shen
collection DOAJ
description Early neuroinflammatory injury plays a crucial role in initiating and progressing multiple sclerosis (MS). Neutrophils are forerunners to neural lesions in MS, yet the temporal alterations of their functions in MS remains unclear. This study demonstrated a positive correlation between circulatory neutrophil counts and disease activity and severity in treatment-naïve MS patients. In experimental autoimmune encephalomyelitis (EAE), we documented the recruitment of neutrophils to spinal cord during the preclinical phase, with these cells contributing to the disruption of the blood-spinal cord barrier (BSCB) during the onset of the disease. Furthermore, during the peak phase, infiltrated neutrophils promoted demyelination through formation of neutrophil extracellular traps (NETs), cytokine secretion and antigen presentation. Notably, the inhibition of neutrophil infiltration using a CXCR2 inhibitor effectively mitigated white matter damage and physical disability, underscoring their potential as therapeutic targets. In conclusion, neutrophils represent promising candidates for both disease treatment and prognosis evaluation in MS. By elucidating their temporal roles and mechanisms of action, we can potentially harness their modulation to improve patient outcomes and disease management.
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spelling doaj-art-120b1e9c7aae4fd79c1af8edf3d3dca72025-08-20T02:37:45ZengElsevierNeurobiology of Disease1095-953X2024-12-0120310674410.1016/j.nbd.2024.106744Temporal dynamics of neutrophil functions in multiple sclerosisShishi Shen0Shilin Wu1Yuge Wang2Li Xiao3Xiaobo Sun4Wenxuan Sun5Yipeng Zhao6Rui Li7Jiaqi Zhang8Zhanhang Wang9Shaoli Zhou10Shixiong Huang11Yanyu Chang12Yaqing Shu13Chen Chen14Zhengqi Lu15Wei Cai16Wei Qiu17Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Guangdong 999 Brain Hospital, Guangzhou, Guangdong 510000, ChinaDepartment of Anesthesiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Hainan Provincial People's Hospital, Haikou, Hainan 570100, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Department of Neurology, The First People's Hospital of Kashi, Kashi, Xinjiang 844000, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, ChinaDepartment of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Corresponding author at: Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Corresponding author at: Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong 510630, China; Department of Neurology, The First People's Hospital of Kashi, Kashi, Xinjiang 844000, China; Corresponding author at: Department of Neurology, Mental and Neurological Disease Research Center, The Third Affiliated Hospital of Sun Yat-sen University, 600 Tianhe Road, Guangzhou, Guangdong 510630, China.Early neuroinflammatory injury plays a crucial role in initiating and progressing multiple sclerosis (MS). Neutrophils are forerunners to neural lesions in MS, yet the temporal alterations of their functions in MS remains unclear. This study demonstrated a positive correlation between circulatory neutrophil counts and disease activity and severity in treatment-naïve MS patients. In experimental autoimmune encephalomyelitis (EAE), we documented the recruitment of neutrophils to spinal cord during the preclinical phase, with these cells contributing to the disruption of the blood-spinal cord barrier (BSCB) during the onset of the disease. Furthermore, during the peak phase, infiltrated neutrophils promoted demyelination through formation of neutrophil extracellular traps (NETs), cytokine secretion and antigen presentation. Notably, the inhibition of neutrophil infiltration using a CXCR2 inhibitor effectively mitigated white matter damage and physical disability, underscoring their potential as therapeutic targets. In conclusion, neutrophils represent promising candidates for both disease treatment and prognosis evaluation in MS. By elucidating their temporal roles and mechanisms of action, we can potentially harness their modulation to improve patient outcomes and disease management.http://www.sciencedirect.com/science/article/pii/S0969996124003462Neutrophil heterogeneityEarly lesionDemyelinationMultiple sclerosisBlood brain barrierAntigen presentation
spellingShingle Shishi Shen
Shilin Wu
Yuge Wang
Li Xiao
Xiaobo Sun
Wenxuan Sun
Yipeng Zhao
Rui Li
Jiaqi Zhang
Zhanhang Wang
Shaoli Zhou
Shixiong Huang
Yanyu Chang
Yaqing Shu
Chen Chen
Zhengqi Lu
Wei Cai
Wei Qiu
Temporal dynamics of neutrophil functions in multiple sclerosis
Neurobiology of Disease
Neutrophil heterogeneity
Early lesion
Demyelination
Multiple sclerosis
Blood brain barrier
Antigen presentation
title Temporal dynamics of neutrophil functions in multiple sclerosis
title_full Temporal dynamics of neutrophil functions in multiple sclerosis
title_fullStr Temporal dynamics of neutrophil functions in multiple sclerosis
title_full_unstemmed Temporal dynamics of neutrophil functions in multiple sclerosis
title_short Temporal dynamics of neutrophil functions in multiple sclerosis
title_sort temporal dynamics of neutrophil functions in multiple sclerosis
topic Neutrophil heterogeneity
Early lesion
Demyelination
Multiple sclerosis
Blood brain barrier
Antigen presentation
url http://www.sciencedirect.com/science/article/pii/S0969996124003462
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