title: Mesenchymal stem cells attenuate ischemic acute kidney injury by inducing regulatory T cells through splenocyte interactions.
abstract: The mechanism of mesenchymal stem cell therapy in acute kidney injury remains uncertain. Previous studies indicated that mesenchymal stem cells could attenuate inflammation-related organ injury by induction of regulatory T cells. Whether regulatory T-cell induction is a potential mechanism of mesenchymal stem cell therapy in ischemic acute kidney injury and how these induced regulatory T cells orchestrate local inflammation are unknown. Here we found that mesenchymal stem cells decrease serum creatinine and urea nitrogen levels, improve tubular injury, and downregulate IFN-γ production of T cells in the ischemic kidney. In addition to the lung, mesenchymal stem cells persisted mostly in the spleen. Mesenchymal stem cells increased the percentage of regulatory T cells in the spleen and the ischemic kidney. Antibody-dependent depletion of regulatory T cells blunted the therapeutic effect of mesenchymal stem cells, while coculture of splenocytes with mesenchymal stem cells caused an increase in the percentage of regulatory T cells. Splenectomy abrogated attenuation of ischemic injury, and downregulated IFN-γ production and the induction of regulatory T cells by mesenchymal stem cells. Thus, mesenchymal stem cells ameliorate ischemic acute kidney injury by inducing regulatory T cells through interactions with splenocytes. Accumulated regulatory T cells in ischemic kidney might be involved in the downregulation of IFN-γ production.
authors.affiliation: State Key Laboratory of Kidney Disease, Department of Nephrology, Chinese PLA General Hospital and Military Medical Postgraduate College, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Rui
authors.initials: R
authors.lastname: Ding
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Cui
authors.forename: Fei
authors.initials: F
authors.lastname: Zhu
authors.forename: Yuansheng
authors.initials: Y
authors.lastname: Xie
authors.forename: Xuefeng
authors.initials: X
authors.lastname: Sun
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.forename: Quan
authors.initials: Q
authors.lastname: Hong
authors.forename: Qinggang
authors.initials: Q
authors.lastname: Li
authors.forename: Suozhu
authors.initials: S
authors.lastname: Shi
authors.forename: Xiaoluan
authors.initials: X
authors.lastname: Liu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D058186:Acute Kidney Injury / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy*; D000818:Animals; D001806:Blood Urea Nitrogen; D002450:Cell Communication / Q000502:physiology*; D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D003404:Creatinine / Q000097:blood; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000378:metabolism; D007668:Kidney / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000473:pathology* / Q000601:surgery; D013156:Splenectomy; D050378:T-Lymphocytes, Regulatory / Q000473:pathology*
chemical_list: D007371:Interferon-gamma; D003404:Creatinine