title: Transcriptional analysis of infiltrating T cells in kidney ischemia-reperfusion injury reveals a pathophysiological role for CCR5.
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 array-based 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.
authors.affiliation: Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Ross Bldg., Rm. 965, 720 Rutland Ave., Baltimore, MD 21205, USA.
authors.forename: Gang Jee
authors.initials: GJ
authors.lastname: Ko
authors.forename: Douglas
authors.initials: D
authors.lastname: Linfert
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Higbee
authors.forename: Tonya
authors.initials: T
authors.lastname: Watkins
authors.forename: Chris
authors.initials: C
authors.lastname: Cheadle
authors.forename: Manchang
authors.initials: M
authors.lastname: Liu
authors.forename: Lorraine
authors.initials: L
authors.lastname: Racusen
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Grigoryev
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
mesh_terms: D000818:Animals; D000906:Antibodies; D017252:CD3 Complex / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D016000:Cluster Analysis; D004797:Enzyme-Linked Immunosorbent Assay; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000502:physiology*; D007668:Kidney / Q000166:cytology / Q000293:injuries* / Q000473:pathology*; D007674:Kidney Diseases / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology*; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000378:metabolism*
chemical_list: D000906:Antibodies; D017252:CD3 Complex; D018925:Chemokines; D019713:Receptors, CCR5