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Abstract: SA-OR018

TLR9 Mediated IL-17A Responses Are Associated with the Pathogenesis of Polymicrobial Septic AKI

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms


  • Naito, Yoshitaka, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Tsuji, Takayuki, NIDDK/NIH, Bethesda, Maryland, United States
  • Fujikura, Tomoyuki, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Ohashi, Naro, Hamamatsu University School of Medicine, Hamamatsu, Japan
  • Kato, Akihiko, Hamamatsu University Hospital, Hamamatsu, Shizuoka, Japan
  • Yasuda, Hideo, Hamamatsu University School of Medicine, Hamamatsu, Japan

Toll-like receptor 9 (TLR9) contributes to the development of polymicrobial septic AKI. Recently, interleukin (IL) -17A has been shown to play a pathogenic role in septic AKI. According to the previous study, TLR 9 mediated IL-17A responses were associated with the pathogenesis of many conditions, including murine hypersensitivity pneumonitis, mycobacteria-elicited pulmonary granuloma, and neurotoxicity induced by microglia. However, its role in septic AKI remains unclear. We hypothesized that TLR9-mediated IL-17A responses are associated with the pathogenesis of polymicrobial septic AKI.


Tlr9-knockout (Tlr9KO) mice and IL-17A knockout mice (IL-17AKO) and both wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) operation to induce polymicrobial sepsis. We performed functional and pathological assessment of the kidney and splenic apoptosis evaluated by immunohistochemistry of caspase 3 at 18 hours after CLP. Survival were assessed for the following 7 days after CLP. We assessed IL-17A consentrations in plasma and ascites from Tlr9KO and WT mice at 3, 6, 18 hours after CLP by enzyme-linked immunosorbent assay (ELISA) also. Furthermore, we examined IL-17A production of immune cells in spleen by flow cytometry.


Although WT mice developed kidney injury at 18 hours after CLP, Tlr9KO and IL-17AKO mice exhibited decreased serum creatinine levels, expression of Kidney Injury Molecule-1 in proximal tubular cells, and improved tubular damage score in cortex. Splenic apoptosis were decreased at 18 hours after CLP in both Tlr9KO and IL-17AKO mice compared with WT mice. Mortalities were less in both Tlr9KO and IL-17AKO mice compared with WT mice after CLP. Furthermore, IL-17 A levels of both plasma and ascites were significantly higher in WT mice than Tlr9KO mice at 18 hours after CLP, and IL-17A levels in ascites tended to increase in earlier phase than in plasma. IL-17A production of splenic γδ T cells was less in Tlr9KO mice compared to WT mice at 3 hours after CLP.


We showed that Tlr9KO and IL-17AKO could protect against polymicrobial septic AKI, and Tlr9KO mice decreased IL-17A secretion in plasma, ascites, and splenic γδ T cells. These findings suggest that TLR9 mediate IL-17A production, and this pathway is associated with the pathogenesis of septic AKI.