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

LIU Pan; XI Deshuang; HUANG Rui; TENG Yilin; LIU Rui; ZENG Gaofeng; ZONG Shao-hui

doi:10.3969/j.issn.1006-5725.2024.08.012

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 treat-ment 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.