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On-line Access: 2023-04-10

Received: 2022-08-22

Revision Accepted: 2022-12-30

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Shaohui ZONG


Gaofeng ZENG


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Journal of Zhejiang University SCIENCE B 2023 Vol.24 No.4 P.312-325


Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells

Author(s):  Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG

Affiliation(s):  Department of Spine Osteopathic, the First Affiliated Hospital of Guangxi Medical University, Nanning 530021, China; more

Corresponding email(s):   xiaohui3008@126.com, fengfeng_388@126.com

Key Words:  Short-chain fatty acids (SCFAs), Spinal cord injury (SCI), Regulatory T cells, IL-17+ γ, δ, T cells, Neuroprotection, Inflammation, Motor function recovery

Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG. Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells[J]. Journal of Zhejiang University Science B, 2023, 24(4): 312-325.

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author="Pan LIU, Mingfu LIU, Deshuang XI, Yiguang BAI, Ruixin MA, Yaomin MO, Gaofeng ZENG, Shaohui ZONG",
journal="Journal of Zhejiang University Science B",
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%T Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells
%A Pan LIU
%A Mingfu LIU
%A Deshuang XI
%A Yiguang BAI
%A Ruixin MA
%A Yaomin MO
%A Gaofeng ZENG
%A Shaohui ZONG
%J Journal of Zhejiang University SCIENCE B
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%D 2023
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2200417

T1 - Short-chain fatty acids ameliorate spinal cord injury recovery by regulating the balance of regulatory T cells and effector IL-17+ γδ T cells
A1 - Pan LIU
A1 - Mingfu LIU
A1 - Deshuang XI
A1 - Yiguang BAI
A1 - Ruixin MA
A1 - Yaomin MO
A1 - Gaofeng ZENG
A1 - Shaohui ZONG
J0 - Journal of Zhejiang University Science B
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PB - Zhejiang University Press & Springer
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DOI - 10.1631/jzus.B2200417

spinal cord injury (SCI) causes motor, sensory, and autonomic dysfunctions. The gut microbiome has an important role in SCI, while short-chain fatty acids (SCFAs) are one of the main bioactive mediators of microbiota. In the present study, we explored the effects of oral administration of exogenous SCFAs on the recovery of locomotor function and tissue repair in SCI. Allen’s method was utilized to establish an SCI model in Sprague-Dawley (SD) rats. The animals received water containing a mixture of 150 mmol/L SCFAs after SCI. After 21 d of treatment, the Basso, Beattie, and Bresnahan (BBB) score increased, the regularity index improved, and the base of support (BOS) value declined. Spinal cord tissue inflammatory infiltration was alleviated, the spinal cord necrosis cavity was reduced, and the numbers of motor neurons and Nissl bodies were elevated. Enzyme-linked immunosorbent assay (ELISA), real-time quantitative polymerase chain reaction (qPCR), and immunohistochemistry assay revealed that the expression of interleukin (IL)‍-10 increased and that of IL-17 decreased in the spinal cord. SCFAs promoted gut homeostasis, induced intestinal t cells to shift toward an anti-inflammatory phenotype, and promoted regulatory T (Treg) cells to secrete IL-10, affecting Treg cells and IL-17+ γ;δ; t cells in the spinal cord. Furthermore, we observed that Treg cells migrated from the gut to the spinal cord region after SCI. The above findings confirm that SCFAs can regulate Treg cells in the gut and affect the balance of Treg and IL-17+ γ;δ; t cells in the spinal cord, which inhibits the inflammatory response and promotes the motor function in SCI rats. Our findings suggest that there is a relationship among gut, spinal cord, and immune cells, and the “gut-spinal cord-immune” axis may be one of the mechanisms regulating neural repair after SCI.

短链脂肪酸通过调节调节性T细胞和IL-17+ γδ T细胞的平衡来改善脊髓损伤的恢复

1广西医科大学第一附属医院脊柱骨科,中国南宁市, 530021
摘要:脊髓损伤可以引起运动、感觉和自主神经功能障碍。肠道微生物组在脊髓损伤中具有重要作用,而短链脂肪酸是微生物群的主要生物活性介质之一。在本研究中,我们探讨了口服外源性短链脂肪酸对脊髓损伤运动功能恢复和组织修复的影响。采用Allen方法建立SD大鼠脊髓损伤模型。脊髓损伤后,动物接受含有150 mmol/L短链脂肪酸混合物的水。治疗21天后,BBB评分升高,步态的规律性指数改善,后肢步宽值下降。脊髓组织炎症浸润减轻,脊髓坏死腔减少,运动神经元和尼氏体数量升高。酶联免疫吸附测定(ELISA)、实时定量聚合酶链反应(qPCR)和免疫组化检测显示脊髓中白细胞介素-10(IL-10)表达升高,IL-17表达降低。短链脂肪酸能促进肠道稳态,诱导肠道T细胞转向抗炎表型,促进调节性T细胞(Treg)分泌IL-10,影响脊髓中的Treg细胞和IL-17+ γδ T细胞。此外,我们观察到脊髓损伤后Treg细胞从肠道迁移到脊髓区域。以上结果证实,短链脂肪酸可调节肠道中的Treg细胞,影响脊髓中Treg和IL-17+ γδ T细胞的平衡,抑制炎症反应,促进脊髓损伤大鼠的运动功能。我们的研究结果表明,肠道、脊髓和免疫细胞之间存在一定的关系,"肠道-脊髓-免疫"轴可能是脊髓损伤后神经修复的调节机制之一。

关键词:短链脂肪酸;脊髓损伤;调节性T细胞;IL-17+ γδ T细胞;神经保护;炎症;运动功能恢复

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


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