Endogenous Toll-Like Receptor 9 Regulates AKI by Promoting Regulatory T Cell Recruitment.
J Am Soc Nephrol
; 27(3): 706-14, 2016 Mar.
Article
in En
| MEDLINE
| ID: mdl-26116356
ABSTRACT
Toll-like receptor 9 (TLR9) enhances proinflammatory responses, but whether it can act in a regulatory capacity remains to be established. In experimental murine AKI induced by cisplatin, Tlr9(-/-) mice developed enhanced renal injury and exhibited fewer intrarenal regulatory T cells (Tregs) compared with genetically intact mice. A series of reconstitution and depletion studies defined a role for TLR9 in maintaining Treg-mediated homeostasis in cisplatin-induced AKI. When Rag1(-/-) mice were reconstituted with nonregulatory CD25(-) splenocytes from wild-type (WT) or Tlr9(-/-) mice, AKI was similarly enhanced. However, when Rag1(-/-) mice were reconstituted with CD4(+)CD25(+) regulatory cells, WT CD4(+)CD25(+) cells were more renoprotective and localized to the kidney more efficiently than Tlr9(-/-) CD4(+)CD25(+) cells. In Treg-depleted Foxp3(DTR) mice, reconstitution with naive WT CD4(+)CD25(+) cells resulted in less severe AKI than did reconstitution with Tlr9(-/-) Tregs. Tlr9(-/-) mice were not deficient in CD4(+)CD25(+) cells, and WT and TLR9-deficient Tregs had similar suppressive function ex vivo. However, expression of adhesion molecules important in Treg trafficking was reduced on peripheral CD4(+)CD25(+) cells from Tlr9(-/-) mice. In conclusion, we identified a pathway by which TLR9 promotes renal Treg accumulation in AKI.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Lymphocyte Activation
/
T-Lymphocytes, Regulatory
/
Toll-Like Receptor 9
/
Acute Kidney Injury
Limits:
Animals
Language:
En
Journal:
J Am Soc Nephrol
Journal subject:
NEFROLOGIA
Year:
2016
Type:
Article