The Journal of Practical Medicine >

2024 , Vol. 40 >Issue 8: 1088 - 1094

DOI: https://doi.org/10.3969/j.issn.1006-5725.2024.08.012

Basic Research

Short⁃chain fatty acids alleviate γδT cell⁃mediated inflammatory response via inhibiting IL⁃17A and NF⁃κB signaling pathway

  • Pan LIU ,
  • Deshuang XI ,
  • Rui HUANG ,
  • Yilin TENG ,
  • Rui LIU ,
  • Gaofeng ZENG ,
  • Shaohui. ZONG
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  • *.Department of Orthopaedics，the Third Affiliated Hospital of Xinxiang Medical College，Xinxiang 453000，China
    *.Department of Spine and Osteopathy，the First Affiliated Hospital of Guangxi Medical University，Nanning 530021，China

Received date: 2023-08-10

  Online published: 2024-04-19

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Abstract

Objective To explore the mechanism of short-chain fatty acids in alleviating γδT cell-mediated inflammatory response. Methods A certain concentration of short-chain fatty acids was used to intervene in rat intestinal-derived γδT cells. CCK-8 was used to detect the effect of shortchain fatty acids on γδT activity. ELISA was used to detect the content of the IL-17A， RT-qPCR was utilized to detect the expression of the IL-17A， and flow cytometry was applied to analyze the IL-17+γδT cell frequency. The effect of SCFAs on IL-17A and NF-κB signaling pathway in γδT cells were observed by Western blot. Results CCK-8 assay showed that the concentration of sodium acetate was less than or equal to 0.5 mmol/L， and the concentrations of sodium propionate， sodium butyrate， and mixed short-chain fatty acids were less than or equal to 0.25 mmol/L， indicating no inhibitory effect on the proliferation of γδT cells. ELISA and RT-qPCR showed that the treatment of γδT cells with sodium propionate， sodium butyrate， and mixed short-chain fatty acids significantly decreased the levels of IL-17A compared with the control group. Flow cytometry revealed a significant decrease in the proportion of IL-17+γδT cells under the treatment of sodium propionate， sodium butyrate， mixed shortchain fatty acids， and TSA intervention. Western blot found that sodium propionate， sodium butyrate， and mixed shortchain fatty acids could inhibit the expression of IL-17A and IKK， as well as the phosphorylation level of NF-κB. Conclusion Shortchain fatty acids could inhibit the activation of IL-17A and NF-κB signaling pathway in γδT cells， thereby alleviating the inflammatory response in the body.

Key words： short-chain fatty acids; γδT cell; IL-17A; NF-κB

Cite this article

Pan LIU , Deshuang XI , Rui HUANG , Yilin TENG , Rui LIU , Gaofeng ZENG , Shaohui. ZONG . Short⁃chain fatty acids alleviate γδT cell⁃mediated inflammatory response via inhibiting IL⁃17A and NF⁃κB signaling pathway[J]. The Journal of Practical Medicine, 2024 , 40(8) : 1088 -1094 . DOI: 10.3969/j.issn.1006-5725.2024.08.012

References

1 WANG L， YAO C Y， CHEN J Y， et al. γδ T Cell in Cerebral Ischemic Stroke： Characteristic， Immunity-Inflammatory Role， and Therapy［J］. Front Neurol， 2022， 31（13）：842212.
2 MENSURADO S， BLANCO-DOMINGUEZ R， SILVA-SANTOS B. The emerging roles of γδ T cells in cancer immunotherapy［J］.Nat Rev Clin Oncol， 2023，20（3）：178-191. doi:10.1038/s41571-022-00722-1
3 JOUDI A M， REYES FLORES C P， SINGER B D. Epigenetic Control of Regulatory T Cell Stability and Function： Implications for Translation ［J］. Front Immunol， 2022， 13：861607. doi:10.3389/fimmu.2022.861607
4 XU P， ZHANG F， CHANG M M， et al. Recruitment of gammadelta T cells to the lesion via the CCL2/CCR2 signaling after spinal cord injury ［J］. J Neuroinflammation， 2021， 18（1）： 64. doi:10.1186/s12974-021-02115-0
5 LIU L X， WANG H Y， CHEN X Y， et al. Gut microbiota： a new insight into neurological diseases［J］. Chin Med J （Engl）， 2023，136（11）：1261-1277. doi:10.1097/cm9.0000000000002212
6 LING Z X， LIU X， CHENG Y W， et al. Gut microbiota and aging［J］. Crit Rev Food Sci Nutr， 2022， 62（13）：3509-3534. doi:10.1080/10408398.2020.1867054
7 CHEN L， WANG J. Gut microbiota and inflammatory bowel diseaset ［J］. WIREs Mech Dis， 2022，14（2）：e1540. doi:10.1002/wsbm.1540
8 FAN Y， PEDERSEN O. Gut microbiota in human metabolic health and disease ［J］. Nat Rev Microbiol， 2021， 19（1）： 55-71. doi:10.1038/s41579-020-0433-9
9 PARADA V D， DE LA FUENTE M K， LANDSKRON G， et al. Short Chain Fatty Acids （SCFAs）-Mediated Gut Epithelial and Immune Regulation and Its Relevance for Inflammatory Bowel Diseases ［J］. Front Immunol， 2019， 10：277. doi:10.3389/fimmu.2019.01486
10 NEY L M， WIPPLINGER M， GROSSMANN M， et al. Short chain fatty acids： key regulators of the local and systemic immune response in inflammatory diseases and infections［J］. Open Biol， 2023，13（3）：230014. doi:10.1098/rsob.230014
11 杨艳青， 李灿委， 杨自忠， 等. 肠道菌群代谢物--短链脂肪酸的研究进展［J］. 实用医学杂志， 2022，38（14）：1834-1837.
12 LIU X F， SHAO J H， LIAO Y T， et al. Regulation of short-chain fatty acids in the immune system［J］. Front Immunol， 2023，5（14）：1186892.
13 RIBOT J C， LOPES N， SILVA-SANTOS B. γδ T cells in tissue physiology and surveillance ［J］. Nat Rev Immunol， 2021， 21（4）： 221-232. doi:10.1038/s41577-020-00452-4
14 CHEN D， GUO Y L， JIANG J H， et al.γδ T cell exhaustion： Opportunities for intervention［J］.J Leukoc Biol， 2022，112（6）：1669-1676. doi:10.1002/jlb.5mr0722-777r
15 ZHONG Q， ZHOU K， LIANG Q L， et al. Interleukin-23 Secreted by Activated Macrophages Drives gammadeltaT Cell Production of Interleukin-17 to Aggravate Secondary Injury After Intracerebral Hemorrhage ［J］. J Am Heart Assoc， 2016， 5（10）：e004340. doi:10.1161/jaha.116.004340
16 WANG J J， ZHU N N， SU X M， et al. Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis［J］.Cells， 2023，12（5）：793. doi:10.3390/cells12050793
17 ZHANG D， JIAN J P， ZHANG Y N， et al. Short-chain fatty acids in diseases［J］. Cell Commun Signal， 2023，21（1）：212. doi:10.1186/s12964-023-01219-9
18 DAI Y， WEI T， SHEN Z， et al. Classical HDACs in the regulation of neuroinflammation ［J］. Neurochem Int， 2021， 150：105182. doi:10.1016/j.neuint.2021.105182
19 ZHANG S J， ZHAN L J， LI X， et al. Preclinical and clinical progress for HDAC as a putative target for epigenetic remodeling and functionality of immune cells［J］. Int J Biol Sci， 2021，17（13）：3381-3400. doi:10.7150/ijbs.62001
20 代仔怡， 武卫东， 梁继芳， 等. 短链脂肪酸平衡在脓毒症治疗中的研究进展［J］. 实用医学杂志， 2022，38（14）：1834-1837. doi:10.3969/j.issn.1006-5725.2022.03.002
21 BARNABEI L， LAPLANTINE E， MBONGO W， et al. NF-κB： At the Borders of Autoimmunity and Inflammation ［J］. Front Immunol， 2021， 12：716469. doi:10.3389/fimmu.2021.716469
22 CAPECE D， VERZELLA D， FLATI I， et al. NF-κB： blending metabolism， immunity， and inflammation［J］. Trends Immunol， 2022，43（9）：757-775. doi:10.1016/j.it.2022.07.004
23 SUN L， WANG L F， BETHANY B M， et al. IL-17： Balancing Protective Immunity and Pathogenesis［J］. J Immunol Res， 2023，12：3360310. doi:10.1155/2023/3360310
24 MILLS KHG. IL-17 and IL-17-producing cells in protection versus pathology［J］. Nat Rev Immunol， 2023，23（1）：38-54. doi:10.1038/s41577-022-00746-9
25 LIU C， YIN Z， FENG T， et al. An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury ［J］. J Ethnopharmacol， 2021， 264：113364. doi:10.1016/j.jep.2020.113364
26 KIM D I， SONG M K， LEE K. Diesel Exhaust Particulates Enhances Susceptibility of LPS-Induced Acute Lung Injury through Upregulation of the IL-17 Cytokine-Derived TGF-beta（1）/Collagen I Expression and Activation of NLRP3 Inflammasome Signaling in Mice ［J］. Biomolecules， 2021， 11（1）：67. doi:10.3390/biom11010067
27 LI T J， ZHAO L L， QIU J， et al. Interleukin-17 antagonist attenuates lung inflammation through inhibition of the ERK1/2 and NF-kappaB pathway in LPS-induced acute lung injury ［J］. Mol Med Rep， 2017， 16（2）： 2225-2232. doi:10.3892/mmr.2017.6837
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