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IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells

 Myung-Gyu Kim  ;  Tai Yeon Koo  ;  Ji-Jing Yan  ;  Eunwon Lee  ;  Kyu Hyun Han  ;  Jong Cheol Jeong  ;  Han Ro  ;  Beom Seok Kim  ;  Sang-Kyung Jo  ;  Kook Hwan Oh  ;  Charles D. Surh  ;  Curie Ahn  ;  Jaeseok Yang 
 Journal of the American Society of Nephrology, Vol.24(10) : 1529-1536, 2013 
Journal Title
 Journal of the American Society of Nephrology 
Issue Date
Animals ; Antibodies, Monoclonal/therapeutic use* ; Antigen-Antibody Complex/physiology* ; Cell Differentiation/immunology* ; Drug Evaluation, Preclinical ; Fibrosis ; Interleukin-2/immunology ; Interleukin-2/physiology* ; Kidney/immunology ; Kidney/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Renal Insufficiency/immunology ; Renal Insufficiency/pathology ; Renal Insufficiency/prevention & control* ; Reperfusion Injury/immunology ; Reperfusion Injury/pathology ; Reperfusion Injury/prevention & control* ; T-Lymphocytes, Regulatory/drug effects ; T-Lymphocytes, Regulatory/immunology* ; T-Lymphocytes, Regulatory/pathology
Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemia-reperfusion injury (IRI), but the isolation and ex vivo expansion of these cells for clinical application remains challenging. Here, we investigated whether the IL-2/anti-IL-2 complex (IL-2C), a mediator of Treg expansion, can attenuate renal IRI in mice. IL-2C administered before bilateral renal IRI induced Treg expansion in both spleen and kidney, improved renal function, and attenuated histologic renal injury and apoptosis after IRI. Furthermore, IL-2C administration reduced the expression of inflammatory cytokines and attenuated the infiltration of neutrophils and macrophages in renal tissue. Depletion of Tregs with anti-CD25 antibodies abrogated the beneficial effects of IL-2C. However, IL-2C-mediated renal protection was not dependent on either IL-10 or TGF-β. Notably, IL-2C administered after IRI also enhanced Treg expansion in spleen and kidney, increased tubular cell proliferation, improved renal function, and reduced renal fibrosis. In conclusion, these results indicate that IL-2C-induced Treg expansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.
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1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
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