Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5

Gang Jee Ko, Douglas Linfert, Hye Ryoun Jang, Elizabeth Higbee, Tonya Watkins, Chris Cheadle, Manchang Liu, Lorraine Racusen, Dmitry N. Grigoryev, Hamid Rabb

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Although T cells have been shown to play a direct role in kidney ischemia-reperfusion injury (IRI), little is known about the underlying mechanisms. We hypothesized that studying the transcriptional responses in kidney-infiltrating T cells would help elucidate novel therapeutic targets for kidney IRI. Unilateral renal pedicle clamping for 45 min was performed in male C57BL/6 mice, and CD3 + T cells were isolated from the kidney and purified. Transcriptional activities of T cell were measured by arraybased PCR compared between ischemic kidneys and contralateral nonischemic kidneys. Among total of 89 genes analyzed, 24, 22, 24, and 37 genes were significantly changed at 6 h, day 3, day 10, and day 28 after IRI. Genes associated with cytokines, chemokines, and costimulatory molecules were upregulated. Pathway analysis identified CC motif chemokine receptor 5 (CCR5) as a candidate pathophysiological pathway. CCR5 upregulation was validated at the protein level, and CCR5 blockade improved renal function after kidney IRI. Using discovery techniques to identify transcriptional responses in purified kidney-infiltrating cells enabled the elucidation of novel mechanisms and therapeutic targets for IRI.

Original languageEnglish
JournalAmerican Journal of Physiology - Renal Physiology
Volume302
Issue number6
DOIs
Publication statusPublished - 2012 Mar 1

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CCR5 Receptors
Reperfusion Injury
T-Lymphocytes
Kidney
Genes
Inbred C57BL Mouse
Chemokines
Constriction
Up-Regulation

Keywords

  • Acute kidney injury
  • Array-based QRT-PCR
  • Chemokine receptor 5
  • T lymphocyte

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5. / Ko, Gang Jee; Linfert, Douglas; Jang, Hye Ryoun; Higbee, Elizabeth; Watkins, Tonya; Cheadle, Chris; Liu, Manchang; Racusen, Lorraine; Grigoryev, Dmitry N.; Rabb, Hamid.

In: American Journal of Physiology - Renal Physiology, Vol. 302, No. 6, 01.03.2012.

Research output: Contribution to journalArticle

Ko, Gang Jee ; Linfert, Douglas ; Jang, Hye Ryoun ; Higbee, Elizabeth ; Watkins, Tonya ; Cheadle, Chris ; Liu, Manchang ; Racusen, Lorraine ; Grigoryev, Dmitry N. ; Rabb, Hamid. / Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5. In: American Journal of Physiology - Renal Physiology. 2012 ; Vol. 302, No. 6.
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