1. IL-10 from dendritic cells but not from T regulatory cells protects against cisplatin-induced nephrotoxicity.
- Author
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Wang, Wei Wei, Wang, Yamei, Li, Kang, Tadagavadi, Raghu, Friedrichs, William E., Budatha, Madhusudhan, and Reeves, W. Brian
- Subjects
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B cells , *SUPPRESSOR cells , *DENDRITIC cells , *CISPLATIN , *NEPHROTOXICOLOGY , *BONE marrow - Abstract
Interleukin-10 (IL-10), a cytokine with anti-inflammatory effects, is produced by renal parenchymal cells and bone marrow derived cells. Both endogenous and exogenous IL-10 are protective in cisplatin-induced acute kidney injury. However, the source of endogenous IL-10 in cisplatin-induced nephrotoxicity is not clear. Bone marrow chimera experiments in IL10-KO mice indicated that bone marrow derived cells were the primary source of IL-10 in cisplatin nephrotoxicity. Cell specific deletion of IL-10 in T regulatory cells and dendritic cells was accomplished using Foxp3 and CD11c driven cre recombination in IL10flox/flox mice, respectively. Upon treatment with cisplatin, both the IL10flox/flox and the Foxp3YFP-Cre x IL10flox/flox mice developed similar degrees of kidney injury. However, mice with the dendritic cell deletion of IL-10 showed more severe structural and functional changes in the kidney compared to the IL10flox/flox mice. These results indicate that IL-10 from dendritic cells but not from T regulatory cells offers significant endogenous protection against cisplatin induced nephrotoxicity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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