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PMID: 20164824 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Regulatory T cells contribute to the protective effect of ischemic preconditioning in the kidney.

Kidney international ·Vol. 77 ·No. 9 ·2010-05-00 ·Pages 771-80

Kinsey GR, Huang L, Vergis AL, Li L, Okusa MD

Abstract

Reperfusion following ischemia is associated with acute kidney injury and inflammation. Using a mouse model, we exposed the kidney to a nonlethal period of ischemia, rendering it refractory to future ischemia-induced dysfunction. This ischemic preconditioning is partially mediated by Treg lymphocytes that suppress immune responses. We found that this maneuver significantly inhibited the accumulation of neutrophils and macrophages, tubular necrosis, and loss of kidney function caused by a subsequent ischemia/reperfusion injury 1 week later. The initial ischemia/reperfusion caused a significant increase in CD4(+)CD25(+)FoxP3(+) and CD4(+)CD25(+)IL-10(+) Treg cells within the kidney at 7 days of reperfusion. Treatment of preconditioned mice with a Treg cell-depleting antibody (PC61) reversed the effect of preconditioning on kidney neutrophil accumulation and partially inhibited the functional and histological protection of preconditioning. Adoptive transfer of Treg cells in naive mice, before ischemia/reperfusion, mimicked the protective and anti-inflammatory effects of ischemic preconditioning on the kidney. These studies highlight the role of Treg cells in ischemic preconditioning.

MeSH Terms
Acute Kidney Injury/complications,immunology,prevention & control Adoptive Transfer Animals Inflammation/complications,immunology Interleukin-10/immunology Ischemia/complications,immunology,pathology Ischemic Preconditioning/methods Kidney/immunology,pathology Male Mice Mice, Inbred C57BL Neutrophils/immunology,pathology Reperfusion Injury/immunology,pathology,prevention & control T-Lymphocytes, Regulatory/immunology,pathology
Chemicals
Interleukin-10
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Kinsey Gilbert R
Division of Nephrology and Center for Immunity, Inflammation and Regenerative Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
Huang Liping
Vergis Amy L
Li Li
Okusa Mark D
References (39)
39 references, click to expand
  1. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells.
    Immunity. 2006 Feb;24(2):179-89 PMID: 16473830
  2. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: role of macrophages.
    Am J Physiol Renal Physiol. 2005 Apr;288(4):F722-31 PMID: 15561971
  3. Dual role of CCR2 during initiation and progression of collagen-induced arthritis: evidence for regulatory activity of CCR2+ T cells.
    J Immunol. 2004 Jan 15;172(2):890-8 PMID: 14707060
  4. Cytotoxic-T-lymphocyte-associated antigen 4 blockade abrogates protection by regulatory T cells in a mouse model of microbially induced innate immune-driven colitis.
    Infect Immun. 2008 Dec;76(12):5834-42 PMID: 18824539
  5. Fractalkine receptor (CX3CR1) inhibition is protective against ischemic acute renal failure in mice.
    Am J Physiol Renal Physiol. 2008 Jan;294(1):F264-71 PMID: 18003857
  6. The chemokine receptors CCR2 and CX3CR1 mediate monocyte/macrophage trafficking in kidney ischemia-reperfusion injury.
    Kidney Int. 2008 Dec;74(12):1526-37 PMID: 18843253
  7. X-linked lymphoreticular disease in the scurfy (sf) mutant mouse.
    Am J Pathol. 1991 Jun;138(6):1379-87 PMID: 2053595
  8. CCR2 signaling contributes to ischemia-reperfusion injury in kidney.
    J Am Soc Nephrol. 2003 Oct;14(10):2503-15 PMID: 14514728
  9. Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury.
    J Am Soc Nephrol. 2009 Aug;20(8):1744-53 PMID: 19497969
  10. Cutting edge: Autoimmune disease in day 3 thymectomized mice is actively controlled by endogenous disease-specific regulatory T cells.
    J Immunol. 2008 Apr 1;180(7):4366-70 PMID: 18354156
  11. Prevention of kidney ischemia/reperfusion-induced functional injury and JNK, p38, and MAPK kinase activation by remote ischemic pretreatment.
    J Biol Chem. 2001 Apr 13;276(15):11870-6 PMID: 11150293
  12. Intercellular adhesion molecule-1-deficient mice are protected against ischemic renal injury.
    J Clin Invest. 1996 Feb 15;97(4):1056-63 PMID: 8613529
  13. T regulatory and primed uncommitted CD4 T cells express CD73, which suppresses effector CD4 T cells by converting 5'-adenosine monophosphate to adenosine.
    J Immunol. 2006 Nov 15;177(10):6780-6 PMID: 17082591
  14. Monocyte chemoattractant protein-1 expression correlates with monocyte infiltration in the post-ischemic kidney.
    Ren Fail. 2002 Nov;24(6):703-23 PMID: 12472194
  15. Acute kidney injury increases risk of ESRD among elderly.
    J Am Soc Nephrol. 2009 Jan;20(1):223-8 PMID: 19020007
  16. Homing to suppress: address codes for Treg migration.
    Trends Immunol. 2005 Dec;26(12):632-6 PMID: 16243583
  17. Regulatory T cell-derived interleukin-10 limits inflammation at environmental interfaces.
    Immunity. 2008 Apr;28(4):546-58 PMID: 18387831
  18. Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury.
    Kidney Int. 2009 Oct;76(7):717-29 PMID: 19625990
  19. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression.
    Blood. 2007 Aug 15;110(4):1225-32 PMID: 17449799
  20. Pattern recognition receptors and differentiation antigens define murine myeloid cell heterogeneity ex vivo.
    Eur J Immunol. 2003 Aug;33(8):2090-7 PMID: 12884282
  21. Role of TGF-Beta in the induction of Foxp3 expression and T regulatory cell function.
    J Clin Immunol. 2008 Nov;28(6):640-6 PMID: 18810612
  22. Regulatory T-cell compartmentalization and trafficking.
    Blood. 2006 Jul 15;108(2):426-31 PMID: 16537800
  23. Rapid recruitment of inflammatory monocytes is independent of neutrophil migration.
    Blood. 2003 Jul 1;102(1):328-35 PMID: 12623845
  24. Identification of the CD4(+) T cell as a major pathogenic factor in ischemic acute renal failure.
    J Clin Invest. 2001 Nov;108(9):1283-90 PMID: 11696572
  25. Protective effects of renal ischemic preconditioning and adenosine pretreatment: role of A(1) and A(3) receptors.
    Am J Physiol Renal Physiol. 2000 Mar;278(3):F380-7 PMID: 10710542
  26. B cell deficiency confers protection from renal ischemia reperfusion injury.
    J Immunol. 2003 Sep 15;171(6):3210-5 PMID: 12960350
  27. Renal ischemia-reperfusion injury and adenosine 2A receptor-mediated tissue protection: the role of CD4+ T cells and IFN-gamma.
    J Immunol. 2006 Mar 1;176(5):3108-14 PMID: 16493070
  28. The reno-vascular A2B adenosine receptor protects the kidney from ischemia.
    PLoS Med. 2008 Jun 24;5(6):e137 PMID: 18578565
  29. Infiltrated macrophages contribute to recovery after ischemic injury but not to ischemic preconditioning in kidneys.
    Transplantation. 2008 Feb 15;85(3):447-55 PMID: 18301336
  30. Compartmentalization of neutrophils in the kidney and lung following acute ischemic kidney injury.
    Kidney Int. 2009 Apr;75(7):689-98 PMID: 19129795
  31. Regulating the immune system: the induction of regulatory T cells in the periphery.
    Arthritis Res Ther. 2004;6(5):215-22 PMID: 15380036
  32. Incomplete depletion and rapid regeneration of Foxp3+ regulatory T cells following anti-CD25 treatment in malaria-infected mice.
    J Immunol. 2007 Apr 1;178(7):4136-46 PMID: 17371969
  33. Maladaptive role of IL-6 in ischemic acute renal failure.
    J Am Soc Nephrol. 2005 Nov;16(11):3315-25 PMID: 16192425
  34. Decreased capacity of immune cells to cause tissue injury mediates kidney ischemic preconditioning.
    J Immunol. 2006 Jun 1;176(11):7015-20 PMID: 16709863
  35. Increased transforming growth factor-beta 1 expression in regenerating rat renal tubules following ischemic injury.
    Am J Physiol. 1996 Mar;270(3 Pt 2):F500-9 PMID: 8780254
  36. Normal mouse kidneys contain activated and CD3+CD4- CD8- double-negative T lymphocytes with a distinct TCR repertoire.
    J Leukoc Biol. 2008 Dec;84(6):1400-9 PMID: 18765477
  37. NKT cell activation mediates neutrophil IFN-gamma production and renal ischemia-reperfusion injury.
    J Immunol. 2007 May 1;178(9):5899-911 PMID: 17442974
  38. Phenotypic and functional characterization of kidney-infiltrating lymphocytes in renal ischemia reperfusion injury.
    J Immunol. 2006 Sep 1;177(5):3380-7 PMID: 16920979
  39. Ischemic preconditioning provides both acute and delayed protection against renal ischemia and reperfusion injury in mice.
    J Am Soc Nephrol. 2006 Nov;17(11):3115-23 PMID: 16988058
Article Info
Journal
Kidney international
Abbr.
Kidney Int
ISSN
1523-1755
DOI
10.1038/ki.2010.12
Published
2010-05-00
Epub
2010-00-17
Pages
771-80
Language
English
Region
United States
NLM ID
0323470
PMCID
PMC2912287
Subset
IM
Grants
NIDDK NIH HHS · T32DK072922-01 · United States
NIDDK NIH HHS · T32 DK072922-01 · United States
NHLBI NIH HHS · P01 HL073361-01A19001 · United States
NIDDK NIH HHS · R01 DK085259 · United States
NIDDK NIH HHS · DK56223 · United States
NIDDK NIH HHS · R01 DK056223-05 · United States
NIDDK NIH HHS · R01 DK062324 · United States
NHLBI NIH HHS · P01HL07336 · United States
NIDDK NIH HHS · R01 DK056223 · United States
NIDDK NIH HHS · R44 DK058413 · United States
NHLBI NIH HHS · P01 HL073361 · United States
NIDDK NIH HHS · R41 DK058413 · United States
NIDDK NIH HHS · R41 DK058413-01 · United States
NIDDK NIH HHS · DK62324 · United States
NIDDK NIH HHS · F32 DK083185 · United States
NIDDK NIH HHS · F32 DK083185-01 · United States
NIDDK NIH HHS · F32DK083185 · United States
NIDDK NIH HHS · R01 DK062324-05 · United States
NIDDK NIH HHS · T32 DK072922 · United States
NIDDK NIH HHS · DK58413 · United States
External Links
PubMed source DOI: 10.1038/ki.2010.12 PMC Full Text View journal details
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