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

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12 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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Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

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