It is well recognized that damage-associated molecular patterns (DAMPs) released from damaged kidney cells initiate post-ischemic inflammation, an essential step in the progression of kidney ischemia-reperfusion injury. However, the mechanism that coordinates this highly specific process in the ischemic kidney remains to be clarified. Previously, we have demonstrated that CD137 of natural killer (NK) cells specifically stimulates CD137 ligand (CD137L) expressed on tubular epithelial cells (TECs) in such a way that TECs produced high levels of CXCR2 chemokines required for neutrophil chemotaxis. We report here that endogenous TLR2 ligands released from ischemic TECs induce expression of CCR5 chemokines in an autocrine manner, thereby promoting recruitment of NK cells. By implantation of CD137L-/- TECs into the kidney capsule of TLR2-/- mice and vice versa, we further show that TLR2-mediated recruitment of NK cells is an uncoupled event occurring independently of CD137L signaling in TECs and sufficient to result in kidney ischemia-reperfusion injury by inducing subsequent recruitment of neutrophils that is dependent upon CD137L signaling in TECs. Therefore, our findings identify TECs as not only a target for kidney damage but also a master regulator that plays a central role in initiation and amplification of acute sterile inflammation inflicting kidney ischemia-reperfusion injury. Clinically important, the signaling pathway of innate receptors in epithelial cells may therefore represent a good target for blocking acute sterile inflammation occurring as a result of tissue damage, including kidney ischemia-reperfusion injury.
To cite this abstract in AMA style:Cho H, Kwon B, Lee J, Cha H, Kim H, Kim A, Koo S, Mittler R. TLR2 Signaling in Epithelial Cells Initiates Sterile Tissue Inflammation through Recruitment of NK Cells in Renal Ischemia Reperfusion Injury [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/tlr2-signaling-in-epithelial-cells-initiates-sterile-tissue-inflammation-through-recruitment-of-nk-cells-in-renal-ischemia-reperfusion-injury/. Accessed March 28, 2020.
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