TY - JOUR
T1 - IL-10 from dendritic cells but not from T regulatory cells protects against cisplatin-induced nephrotoxicity
AU - Wang, Wei Wei
AU - Wang, Yamei
AU - Li, Kang
AU - Tadagavadi, Raghu
AU - Friedrichs, William E.
AU - Budatha, Madhusudhan
AU - Reeves, W. Brian
N1 - Funding Information:
This work was supported in part by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (DK-081876 and DK-108185) to W.B.R. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.
Publisher Copyright:
© 2020 Wang et al.
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0238816
DO - 10.1371/journal.pone.0238816
M3 - Article
C2 - 32898157
AN - SCOPUS:85090729492
SN - 1932-6203
VL - 15
JO - PloS one
JF - PloS one
IS - 9 September
M1 - e0238816
ER -