Regulatory T Cells Suppress Innate Immunity in Kidney Ischemia-Reperfusion Injury
AUTOR(ES)
Kinsey, Gilbert R.
FONTE
American Society of Nephrology
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2723989Documentos Relacionados
- Kidney ischemia-reperfusion injury induces caspase-dependent pulmonary apoptosis
- Apoptosis and Histopathology of the Heart after Renal Ischemia-Reperfusion in Male Rat Running title: Ischemia-Reperfusion Injury
- Erratum: Apoptosis and Histopathology of the Heart after Renal Ischemia-Reperfusion in Male Rat Running title: Ischemia-Reperfusion Injury
- Remifentanil protects uterus against ischemia-reperfusion injury in rats
- Expression of the RNA-stabilizing protein HuR in ischemia-reperfusion injury of rat kidney