Open AccessIL-10 from dendritic cells but not from T regulatory cells protects against cisplatin-induced nephrotoxicity
Author(s) -
Wei Wei Wang,
Yamei Wang,
Kang Li,
Raghu Tadagavadi,
William E. Friedrichs,
Madhusudhan Budatha,
W. Brian Reeves
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0238816
Subject(s) - cisplatin , nephrotoxicity , bone marrow , foxp3 , endogeny , dendritic cell , chemistry , cd11c , cancer research , cytokine , kidney , biology , immunology , medicine , immune system , endocrinology , chemotherapy , biochemistry , phenotype , gene
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 IL10 flox/flox mice, respectively. Upon treatment with cisplatin, both the IL10 flox/flox and the Foxp3 YFP-Cre x IL10 flox/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 IL10 flox/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.