| First Author | Zhang H | Year | 2022 |
| Journal | J Leukoc Biol | Volume | 112 |
| Issue | 2 | Pages | 233-241 |
| PubMed ID | 34766371 | Mgi Jnum | J:327541 |
| Mgi Id | MGI:7330307 | Doi | 10.1002/JLB.1A0821-466R |
| Citation | Zhang H, et al. (2022) Effects of TNF-alpha deletion on iNKT cell development, activation, and maturation in the steady-state and chronic alcohol-consuming mice. J Leukoc Biol 112(2):233-241 |
| abstractText | Cytokines play critical roles in regulating iNKT cell development, activation, and maturation. TNF-alpha co-occurs with iNKT cells in steady-state and many disease conditions. How TNF-alpha affects iNKT cell function has not been thoroughly investigated. It was found that chronic alcohol consumption enhanced iNKT cell activation and maturation. The underlying mechanism is not known. Herein, a TNF-alpha KO mouse model was used to address these issues. It was found that the depletion of TNF-alpha mitigated alcohol consumption-enhanced iNKT cell activation and maturation. In steady-state, depletion of TNF-alpha 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-alpha KO mice, suggesting that depletion of TNF-alpha impairs iNKT cell development and maturation. The percentage of CD69(+) iNKT cells was significantly lower in the thymus, spleen, and liver of TNF-alpha KO mice compared to their wild-type littermates, suggesting that depletion of TNF-alpha inhibits iNKT cell activation. Moreover, the percentage of splenic IL-4- and IFN-gamma-producing iNKT cells was significantly lower in TNF-alpha KO mice than in their wild-type littermates. The depletion of TNF-alpha increased PLZF(+) iNKT cells in the thymus and down-regulated the expression of CD122 on iNKT cells. Collectively, these results support that TNF-alpha 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-alpha. |
