Regulatory T cells suppress innate immunity in kidney ischemia-reperfusion injury.
Both innate and adaptive mechanisms participate in the pathogenesis of kidney ischemia-reperfusion injury (IRI), but the role of regulatory immune mechanisms is unknown. We hypothesized that the anti-inflammatory effects of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) protect against renal IRI. Partial depletion of Tregs with an anti-CD25 mAb potentiated kidney damage induced by IRI. Reducing the number of Tregs resulted in more neutrophils, macrophages, and innate cytokine transcription in the kidney after IRI but did not affect CD4(+) T cells or B cells. We performed adoptive transfer of lymph node cells from wild-type mice or FoxP3-deficient Scurfy mice into T cell- and B cell-deficient RAG-1 knockout mice to generate mice with and without FoxP3(+) Tregs, respectively. FoxP3(+) Treg-deficient mice accumulated a greater number of inflammatory leukocytes after renal IRI than mice containing Tregs. To confirm that a lack of Tregs potentiated renal injury, we co-transferred isolated Tregs and Scurfy lymph node cells; Treg repletion significantly attenuated IRI-induced renal injury and leukocyte accumulation. Furthermore, although adoptive transfer of wild-type Tregs into RAG-1 knockout mice was sufficient to prevent kidney IRI, transfer of IL-10-deficient Tregs was not. Taken together, these results demonstrate that Tregs modulate injury after kidney IRI through IL-10-mediated suppression of the innate immune system.
Kinsey
Gilbert R
GR
Division of Nephrology, University of Virginia Health System, Charlottesville, VA 22908, USA.
Sharma
Rahul
R
Huang
Liping
L
Li
Li
L
Vergis
Amy L
AL
Ye
Hong
H
Ju
Shyr-Te
ST
Okusa
Mark D
MD
D019264:Adoptive Transfer; D000818:Animals; D007113:Immunity, Innate; D016753:Interleukin-10 / Q000378:metabolism*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D007674:Kidney Diseases / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10