Foxp3+ regulatory T cells participate in repair of ischemic acute kidney injury
- Authors
- Gandolfo M.T.; Jang H.R.; Bagnasco S.M.; Ko G.-J.; Agreda P.; Satpute S.R.; Crow M.T.; King L.S.; Rabb H.
- Issue Date
- 2009
- Keywords
- Ischemia-reperfusion; Lymphocytes; Renal protection
- Citation
- Kidney International, v.76, no.7, pp 717 - 729
- Pages
- 13
- Indexed
- SCOPUS
- Journal Title
- Kidney International
- Volume
- 76
- Number
- 7
- Start Page
- 717
- End Page
- 729
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/16575
- DOI
- 10.1038/ki.2009.259
- ISSN
- 0085-2538
1523-1755
- Abstract
- T lymphocytes modulate early ischemia-reperfusion injury in the kidney; however, their role during repair is unknown. We studied the role of TCRΒ 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 TCRΒ CD4 and TCRΒ 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-α generation by TCRΒ CD4 T cells at 10 days. In separate mice, infusion of CD4 CD25 Tregs 1 day after initial injury reduced INF-γ production by TCRΒ 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. © 2009 Inernational Society of Nephrology.
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Collections - 2. Clinical Science > Department of Nephrology and Hypertension > 1. Journal Articles
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