Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury

Gang Jee Ko, Hye Ryoun Jang, Yanfei Huang, Karl L. Womer, Manchang Liu, Elizabeth Higbee, Zuoxiang Xiao, Hideo Yagita, Lorraine Racusen, Abdel Rahim A Hamad, Hamid Rabb

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Inflammation contributes to the pathogenesis of ischemic acute kidney injury (AKI), and T cells mediate the early phase of ischemia-reperfusion injury (IRI). The Fas/Fas ligand (FasL) pathway modulates the balance of T cell subsets in the peripheral circulation as well as multiple inflammatory responses, suggesting that FasL may mediate ischemic AKI. Here, we induced bilateral renal IRI in mice bearing a loss-of-function mutation of FasL (the gld mutation) and in wild-type mice. Compared with wild-type mice, serum creatinine was lower in gld mice (1.4 ± 0.9 mg/dl versus 2.6 ± 0.4) at 24 hours after IRI (P < 0.05). In addition, gld mice had fewer TNF-α-producing T lymphocytes in the kidneys and renal lymph nodes. Furthermore, pharmacologic blockade of FasL protected the kidneys of wild-type mice from IRI. Analysis of bone marrow chimeric mice suggested that the pathogenic effect of FasL involves leukocytes; reconstitution of wild-type mice with gld splenocytes attenuated IRI. In contrast, reconstitution of gld mice with wild-type splenocytes enhanced IRI. These data demonstrate that FasL, particularly on leukocytes, mediates ischemic AKI.

Original languageEnglish
Pages (from-to)732-742
Number of pages11
JournalJournal of the American Society of Nephrology
Issue number4
Publication statusPublished - 2011 Apr 1


ASJC Scopus subject areas

  • Nephrology

Cite this

Ko, G. J., Jang, H. R., Huang, Y., Womer, K. L., Liu, M., Higbee, E., Xiao, Z., Yagita, H., Racusen, L., Hamad, A. R. A., & Rabb, H. (2011). Blocking fas ligand on leukocytes attenuates kidney ischemia-reperfusion injury. Journal of the American Society of Nephrology, 22(4), 732-742.