Interleukin-15 prevents concanavalin A-induced liver injury in mice via NKT cell-dependent mechanism.
Administration of concanavalin A (Con A) induces a rapid and severe liver injury in mice. Natural killer T (NKT) cells are recognized to be the key effector cells, and a variety of cytokines [e.g., interleukin 4 (IL-4), IL-5, interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha)] have been shown to play vital roles in Con A-induced liver injury, whereas the role of IL-15, a critical cytokine in the development and homeostasis of NKT cells, remains obscure. In this study, pretreatment with IL-15 prevented mice from Con A-induced mortality, elevation of serum transaminase, liver necrosis, and hepatocyte apoptosis. Depletion of NKT cells abolished Con A-induced liver injury, which could be restored by adoptive transfer of purified NKT cells but not by that of in vivo or in vitro IL-15-treated hepatic NKT cells. Furthermore, transfer of wild-type NKT cells to CD1d-/- mice restored liver injury, whereas transfer of IL-15-treated NKT cells did not. IL-15 pretreatment decreased the NKT-derived IL-4, IL-5, and TNF-alpha production, thereby resulting in less infiltration of eosinophils, which play a critical role in Con A-induced liver injury. In conclusion, IL-15 protects against Con A-induced liver injury via an NKT cell-dependent mechanism by reducing their production of IL-4, IL-5, and infiltration of eosinophils. These findings suggest that IL-15 may be of therapeutic relevance in human autoimmune-related hepatitis.
Li
Bofeng
B
Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei 230027, China.
Sun
Rui
R
Wei
Haiming
H
Gao
Bin
B
Tian
Zhigang
Z
D000818:Animals; D001707:Biopsy, Needle; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology* / Q000517:prevention & control; D003208:Concanavalin A; D016207:Cytokines / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism*; D019409:Interleukin-15 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011336:Probability; D012016:Reference Values; D012680:Sensitivity and Specificity
D016207:Cytokines; D018836:Inflammation Mediators; D019409:Interleukin-15; D003208:Concanavalin A