Trichostatin A attenuates E.coli-induced inflammation by modulating CD4+T cell homeostasis
10.16016/j.2097-0927.202507014
- VernacularTitle:曲古抑菌素A通过重塑CD4+T细胞免疫稳态缓解大肠杆菌感染性炎症
- Author:
Yu XIA
1
;
Jing YU
;
Daiqi CHEN
;
Guochang LIU
;
Yun WANG
;
Jun YAN
Author Information
1. 陆军军医大学大坪医院特殊环境战伤防治研究室
- Keywords:
trichostatin A(TSA);
CD4+T cells;
Escherichia coli;
infectious inflammation
- From:
Journal of Army Medical University
2025;47(21):2591-2601
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the role of trichostatin A(TSA)in regulating CD4+T cell subpopulations during Escherichia coli(E.coli)inflammatory infections.Methods Male mice(8 weeks old,weighing 22～25 g)were randomly divided into 3 groups(n=16):a dimethyl sulfoxide(DMSO)control group,an infection group(DMSO+E.coli),and an intervention group(E.coli+TSA).E.coli was administered via intraperitoneal injection at a concentration of 3×10? CFU/mL to establish an infection model.The E.coli+TSA group was further subdivided into 3 subgroups based on different TSA concentrations(2.5,5.0,10.0 mg/kg).Then the samples were collected at different time points(12,24,48,96 h)after TSA intervention.The efficacy of TSA in treating E.coli-induced inflammatory responses and its relationship with CD4+T cell subsets were evaluated by survival rate observation,body weight monitoring,histopathological staining for small intestine,ELISA detection,transcriptomics sequencing,flow cytometry and RT-qPCR analysis.Results Compared with the E.coli group,5 mg/kg TSA significantly increased survival rate,suppressed body weight loss,improved pathological damage in the small intestinal,reduced serum TNF-α level in 24 h after infection(P<0.000 1),and elevated IL-10 level(P<0.05).Transcriptomic analysis revealed that 5 mg/kg TSA intervention for 24 h modulated the T cell differentiation signaling pathways,including those regulating FoxO,Th17,and Th1/2.Flow cytometry and RT-qPCR results showed that compared to the E.coli group,5 mg/kg TSA down-regulated the expression of the Th17 cell marker RORγt in mice 96 h after infection while significantly up-regulated the expression of the Treg cell marker Foxp3(P<0.05).Conclusion TSA may alleviate bacterial infectious inflammatory diseases by regulating the differentiation of CD4+T cells toward the Treg subset while simultaneously inhibiting their differentiation toward the Th17 subset,thereby suppressing the release of proinflammatory cytokines.
