Full
Outline
To investigate the role of trichostatin A (TSA) in regulating CD4+T cell subpopulations during Escherichia coli (E.coli) inflammatory infections.
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 3×10⁸ 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.
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).
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.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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