Effects of TNF-α deletion on iNKT cell development, activation, and maturation in the steady-state and chronic alcohol-consuming mice.
Effects of TNF-α deletion on iNKT cell development, activation, and maturation in the steady-state and chronic alcohol-consuming mice.
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DOI：
10.1002/jlb.1a0821-466r
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发表时间：
2022-08
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
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作者：
细胞因子在调节iNKT细胞的发育、激活和成熟中起着至关重要的作用。TNF-α在稳态和许多疾病条件下与iNKT细胞共同发生。TNF-α如何影响iNKT细胞功能尚未被彻底研究。我们发现，长期饮酒增强了iNKT细胞的激活和成熟。潜在的机制尚不清楚。在此，我们使用TNF-α KO小鼠模型来解决这些问题。我们发现TNF-α的消耗减轻了酒精消耗增强的iNKT细胞激活和成熟。在稳态下，TNF-α的缺失不影响胸腺和脾脏iNKT细胞的频率，但降低肝脏iNKT细胞的频率，增加肝脏iNKT细胞的凋亡。TNF-α KO小鼠胸腺中2期未成熟iNKT细胞比例增加，3期成熟iNKT细胞比例减少，提示TNF-α的缺失损害了iNKT细胞的发育和成熟。与野生型小鼠相比，TNF-α KO小鼠胸腺、脾脏和肝脏中CD69+ iNKT细胞的百分比显著降低，这表明TNF-α的消耗抑制了iNKT细胞的活化。此外，TNF-α KO小鼠脾脏中产生IL-4-和IFN-γ-的iNKT细胞的百分比明显低于野生型小鼠。TNF-α的缺失增加了胸腺PLZF+ iNKT细胞的表达，下调了iNKT细胞上CD122的表达。总的来说，这些结果支持TNF-α在调节iNKT细胞的发育、激活和成熟中起着至关重要的作用，并且酒精消耗通过TNF-α增强iNKT细胞的激活和成熟。TNF-α在iNKT细胞的发育、激活和成熟中起重要作用，慢性饮酒通过TNF-α增强iNKT细胞的激活和成熟。
Cytokines play critical roles in regulating iNKT cell development, activation, and maturation. TNF-α cooccurs with iNKT cells in steady-state and many disease conditions. How TNF-α affects iNKT cell function has not been thoroughly investigated. We found that chronic alcohol consumption enhanced iNKT cell activation and maturation. The underlying mechanism is not known. Herein, we used a TNF-α KO mouse model to address these issues. We found that the depletion of TNF-α mitigated alcohol consumption-enhanced iNKT cell activation and maturation. In steady-state, depletion of TNF-α did not affect the frequency of iNKT cells in the thymus and spleen but decreased iNKT cells in the liver and increased liver iNKT cell apoptosis. The portion of stage-2 immature iNKT cells increased, stage-3 mature iNKT cells decreased in the thymus of TNF-α KO mice, suggesting that depletion of TNF-α impairs iNKT cell development and maturation. The percentage of CD69+ iNKT cells was significantly lower in the thymus, spleen, and liver of TNF-α KO mice compared to their wild-type littermates, suggesting that depletion of TNF-α inhibits iNKT cell activation. Moreover, the percentage of splenic IL-4- and IFN-γ-producing iNKT cells was significantly lower in TNF-α KO mice than in their wild-type littermates. The depletion of TNF-α increased PLZF+ iNKT cells in the thymus and downregulated the expression of CD122 on iNKT cells. Collectively, these results support that TNF-α plays a vital role in the regulation of iNKT cell development, activation, and maturation, and alcohol consumption enhances iNKT cell activation and maturation through TNF-α. TNF-α plays an important role in iNKT cell development, activation and maturation, and chronic alcohol consumption enhances iNKT cell activation and maturation through TNF-α.
影响因子：
4.6
作者：
Kumar A;Gordy LE;Bezbradica JS;Stanic AK;Hill TM;Boothby MR;Van Kaer L;Joyce S
通讯作者：
Joyce S