TY - JOUR
T1 - IL-2/anti-IL-2 complex attenuates renal ischemia-reperfusion injury through expansion of regulatory T cells
AU - Kim, Myung Gyu
AU - Koo, Tai Yeon
AU - Yan, Ji Jing
AU - Lee, Eunwon
AU - Han, Kyu Hyun
AU - Jeong, Jong Cheol
AU - Ro, Han
AU - Kim, Beom Seok
AU - Jo, Sang Kyung
AU - Oh, Kook Hwan
AU - Surh, Charles D.
AU - Ahn, Curie
AU - Yang, Jaeseok
PY - 2013/10
Y1 - 2013/10
N2 - Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemiareperfusion 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-10or TGF-b. Notably, IL-2Cadministered 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 Tregexpansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.
AB - Regulatory T cells (Tregs) can suppress immunologic damage in renal ischemiareperfusion 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-10or TGF-b. Notably, IL-2Cadministered 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 Tregexpansion attenuates acute renal damage and improves renal recovery in vivo, suggesting that IL-2C may be a therapeutic strategy for renal IRI.
UR - http://www.scopus.com/inward/record.url?scp=84885048272&partnerID=8YFLogxK
U2 - 10.1681/ASN.2012080784
DO - 10.1681/ASN.2012080784
M3 - Article
C2 - 23833258
AN - SCOPUS:84885048272
SN - 1046-6673
VL - 24
SP - 1529
EP - 1536
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 10
ER -