Abstract:
:T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRbeta(+)CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), known to blunt immune responses, in repair after ischemia-reperfusion injury to the kidney. Using a murine model of ischemic acute kidney injury we found that there was a significant trafficking of Tregs into the kidneys after 3 and 10 days. Post-ischemic kidneys had increased numbers of TCRbeta(+)CD4(+) and TCRbeta(+)CD8(+) T cells with enhanced pro-inflammatory cytokine production. Treg depletion starting 1 day after ischemic injury using anti-CD25 antibodies increased renal tubular damage, reduced tubular proliferation at both time points, enhanced infiltrating T lymphocyte cytokine production at 3 days and TNF-alpha generation by TCRbeta(+)CD4(+) T cells at 10 days. In separate mice, infusion of CD4(+)CD25(+) Tregs 1 day after initial injury reduced INF-gamma production by TCRbeta(+)CD4(+) T cells at 3 days, improved repair and reduced cytokine generation at 10 days. Treg manipulation had minimal effect on neutrophil and macrophage infiltration; Treg depletion worsened mortality and serum creatinine, while Treg infusion had a late beneficial effect on serum creatinine in bilateral ischemia. Our study demonstrates that Tregs infiltrate ischemic-reperfused kidneys during the healing process promoting repair, likely through modulation of pro-inflammatory cytokine production of other T cell subsets. Treg targeting could be a novel therapeutic approach to enhance recovery from ischemic acute kidney injury.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Gandolfo MT,Jang HR,Bagnasco SM,Ko GJ,Agreda P,Satpute SR,Crow MT,King LS,Rabb Hdoi
10.1038/ki.2009.259subject
Has Abstractpub_date
2009-10-01 00:00:00pages
717-29issue
7eissn
0085-2538issn
1523-1755pii
S0085-2538(15)54050-7journal_volume
76pub_type
杂志文章abstract::In landmark clinical trials, pharmacological inhibition of the renin-angiotensin system (RAS) with angiotensin-converting enzyme inhibitors (ACEIs) attenuated the decline in renal function associated with chronic renal disease (CRD). Hemodynamic and nonhemodynamic effects of angiotensin II (Ang II) attest to its centr...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2000.00031.x
更新日期:2000-05-01 00:00:00
abstract::Cells from RCCT-28A cell line, which exhibited the highest peanut-lectin binding capacity [RCCT-28A(P+)] were separated and cultured attempting to obtain a population of HCO3- secreting cells. The mechanisms of apical solution acid or base extrusion were studied in confluent monolayers. In RCCT-28A (P+) cells net H+ f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.30
更新日期:1993-01-01 00:00:00
abstract::Few studies have examined tubular function after subtotal nephrectomy (Nx) and conservative treatments. The effects of 70% and 80% Nx (associated with dietary phosphate restriction in the latter case) on the apical brush border membrane (BBM) enzymes 5'-nucleotidase, gamma glutamyl-transferase and alkaline-phosphatase...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.485
更新日期:1997-12-01 00:00:00
abstract::In male Wistar rats, renal adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were measured by 31phosphorus nuclear magnetic resonance (31P NMR) and correlated with renal function before, during, and for one hour after a period of 30 to 40 minutes hemorrhagic hypotension. In animals which suff...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.192
更新日期:1986-09-01 00:00:00
abstract:BACKGROUND:The next phase of the molecular revolution will bring functional genomics down to the level of individual cells in a tissue. Laser capture microdissection (LCM) coupled with reverse transcription-polymerase chain reaction (RT-PCR) can measure gene expression in normal, cancerous, injured, or fibrotic tissue....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00295.x
更新日期:2000-09-01 00:00:00
abstract::Tubulointerstitial nephritis (TIN) is a disease pattern with heterogeneous causes. Recently a specific subtype of autoimmune TIN, IgG4-related TIN, has been identified that is part of systemic IgG4-related disease/ autoimmune pancreatitis. On biopsy, this TIN shows an IgG4+ plasma cell-rich infiltrate, akin to the pan...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2010.342
更新日期:2010-11-01 00:00:00
abstract::Healthy male rats were exposed to a chronic ingesta of an isotonic NaCl solution during a period of four months. Two different preparations were utilized to study the effect of this treatment on the active mechanisms of Na+ reabsorption of kidney proximal tubular cells: outermost kidney cortex slices (rich in proximal...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.216
更新日期:1986-10-01 00:00:00
abstract::A new study in dialysis patients demonstrates that more than one-third of rehospitalizations within 30 days of discharge occur within the first week, and these rehospitalizations are associated with worse survival. Imposing a penalty on the dialysis provider for these rehospitalizations, as mandated by the Hospital Re...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.04.046
更新日期:2017-10-01 00:00:00
abstract::To determine whether acute renal failure (ARF) increases the long-term risk of progressive chronic kidney disease (CKD), we studied the outcome of patients whose initial kidney function was normal or near normal but who had an episode of dialysis-requiring ARF and did not develop end-stage renal disease within 30 days...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.289
更新日期:2009-10-01 00:00:00
abstract::Mutations in the MYH9 gene, coding for the non-muscle myosin heavy chain IIA (NMHC-IIA), are responsible for syndromes characterized by macrothrombocytopenia associated with deafness, cataracts, and severe glomerular disease. Electron microscopy of renal biopsies from these patients found glomerular abnormalities char...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.256
更新日期:2011-11-01 00:00:00
abstract::Dihydrotestosterone (DHT) binding studies and the effects of DHT on the expression of beta-glucuronidase (Gus) and kidney androgen-regulated protein (KAP) genes and cell growth were investigated in immortalized early PKSV-PCT and late PKSV-PR proximal tubule cells, derived from transgenic mice carrying the L-pyruvate ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00721.x
更新日期:1998-01-01 00:00:00
abstract::Aboriginal dialysis patients have reduced access to kidney transplantation. The reasons for this disparity are unknown. Tonelli et al. show that in Canada, residence location does not significantly impact on an Aboriginal dialysis patient's likelihood of receiving kidney transplantation. This Commentary explores the i...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5001762
更新日期:2006-09-01 00:00:00
abstract::Mineral metabolism in chronic kidney disease is attracting intense interest and unprecedented levels of research. The pharmaceutical industry has responded by developing various new agents. Bervoets et al. report the use of an unusual combination of basic-science techniques to increase understanding of the kinetics of...
journal_title:Kidney international
pub_type: 评论,杂志文章,评审
doi:10.1038/ki.2008.627
更新日期:2009-02-01 00:00:00
abstract::Mice chronically infected with the virus of lymphocytic choriomeningitis (LCM) develop immune complex glomerulonephritis. Others have shown that adoptive immunization of these mice by the i.p. injection of syngeneic immune spleen cells terminates the chronic viral carrier state. The present studies were designed to de...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1977.49
更新日期:1977-05-01 00:00:00
abstract::[Arg(8)]-vasopressin (AVP) has several functions via its three distinct receptors, V1a, V1b, and V2. The V1a vasopressin receptor (V1aR) is expressed in blood vessels and involved in vascular contraction. Recently, we generated V1a receptor-deficient (V1aR(-/-)) mice and found that they were hypotensive. In addition, ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.319
更新日期:2009-11-01 00:00:00
abstract::Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.122
更新日期:1983-07-01 00:00:00
abstract::It is known that in rodents recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor (rhIGF-1) increase renal mass. It is uncertain, however, whether renal mass increases in proportion to body growth, or whether renal growth is stimulated selectively. In 120 to 150 g female Sprague-Dawl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.376
更新日期:1993-12-01 00:00:00
abstract::Insulin resistance has been associated with kidney disease even in the absence of diabetes; however, pathways linking insulin resistance to kidney disease are unclear. The purpose of this study was to determine if transforming growth factor (TGF)-beta1, a key cytokine associated with kidney disease, responds to circul...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.109
更新日期:2010-08-01 00:00:00
abstract::Intravital multiphoton microscopy is a powerful tool to study kidney physiology in living animals. However, certain technical issues have curbed its usage to date, including limited depth of tissue penetration and high background emission of endogenous signals. Most previous studies have used the excitation range 700–...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.323
更新日期:2016-03-01 00:00:00
abstract::We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208 type ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000377
更新日期:2006-06-01 00:00:00
abstract::Copy number variations associate with different developmental phenotypes and represent a major cause of congenital anomalies of the kidney and urinary tract (CAKUT). Because rare pathogenic copy number variations are often large and contain multiple genes, identification of the underlying genetic drivers has proven to...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.239
更新日期:2015-12-01 00:00:00
abstract:BACKGROUND:Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00271.x
更新日期:1999-02-01 00:00:00
abstract:BACKGROUND:Recent clinical trials of mycophenolate mofetil (MMF) in chronic allograft nephropathy (CAN) demonstrated that the dose of cyclosporine A (CsA) is one of the critical factors in determining graft function in CAN, but the effect of MMF on chronic CsA nephropathy is undetermined. We undertook this study to eva...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00400.x
更新日期:2002-07-01 00:00:00
abstract::Defective recycling of megalin consequent to impaired phosphatidylinositol metabolism has been implicated as a mechanism causing tubular proteinuria in patients with Lowe syndrome. In this issue, Berquez et al. describe an innovative approach using a clinically approved drug to "rebalance" phosphatidylinositols and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2020.06.018
更新日期:2020-10-01 00:00:00
abstract::Macrophages are inflammatory cells with important roles in the propagation of renal injury. More recently they have also been shown to be important in the resolution of inflammation. Wang et al. show that macrophages can be modulated ex vivo by cytokine stimulation, localize to renal tissue, and slow progression of ex...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5002332
更新日期:2007-08-01 00:00:00
abstract::Viral peritonitis is an exceptionally rare occurrence in peritoneal dialysis. In fact, up to now, only one case report has been documented in the literature. In a prospective study, peritoneal dialysis effluent (PDE) was specifically cultured for the following viruses: the herpes group of viruses, including herpes sim...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.191
更新日期:1989-08-01 00:00:00
abstract:BACKGROUND:Renal anemia is an important determinant for left ventricular hypertrophy in dialysis patients and an independent prognosis parameter for the cardiovascular survival in dialysis patients. In addition, an autonomic dysfunction is associated with the uremic state and influences the cardiovascular risk in patie...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1111/j.1523-1755.2004.00810.x
更新日期:2004-08-01 00:00:00
abstract::Effect of varying concentrations (0 to 800 microM) of three different light chains on sodium-dependent L-(14C)alanine and D-(14C)glucose uptake by rat renal brush border membrane vesicles were studied. One kappa and two lambda type light chains (lambda-1 and lambda-2) were isolated from urines of patients with multipl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.237
更新日期:1986-11-01 00:00:00
abstract::Podocytes are highly differentiated cells that play an important role in maintaining glomerular filtration barrier integrity; a function regulated by small GTPase proteins of the Rho family. To investigate the role of Rho A in podocyte biology, we created transgenic mice expressing doxycycline-inducible constitutively...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.472
更新日期:2012-06-01 00:00:00
abstract::In Australia, Canada, New Zealand, and the United States indigenous people have high rates of chronic kidney disease but poor access to effective therapies. To more fully define these issues, we compared the demographics of renal transplantation of indigenous patients in these 4 countries. Data encompassing 312,507 in...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.236
更新日期:2009-09-01 00:00:00