What can tubular progenitor cultures teach us about kidney regeneration?  Paola Romagnani, Hans-Joachim Anders  Kidney International  Volume 83, Issue 3, Pages 351-353 (March 2013) DOI: 10.1038/ki.2012.437 Copyright © 2013 International Society of Nephrology Terms and Conditions

Figure 1 Toll-like receptors drive tubular regeneration via direct and indirect mechanisms. Acute kidney injury usually involves death of differentiated tubular epithelial cells (TECs, yellow). TEC death implies the release of damage-associated molecular patterns (DAMPs) from intracellular compartments into the extracellular space, where they can activate Toll-like receptors (TLRs) and potentially other innate pattern recognition receptors on adjacent cells that survive the triggering insult. Renal tubular progenitors (orange) have a high capacity to survive injuries and, therefore, get positively selected among the surviving cells inside the tubular compartment. Sallustio et al.5 demonstrate that renal tubular progenitor-mediated tubular regeneration is driven by direct TLR2 activation at the renal progenitor surface, which implies a pro-regeneratory role of DAMPs with TLR2 agonistic activity in vivo. As a second, indirect, pathway, DAMPs with agonistic activity on TLR4 on the surface of renal dendritic cells (DCs) in the interstitial compartment trigger the paracrine release of interleukin-22 (IL-22), which fosters tubular regeneration via the IL-22R/STAT3/ERK signaling pathway. This way tubular-cell death drives tubular regeneration via signaling platforms previously considered to exclusively mediate renal immunopathology rather than renal repair. Kidney International 2013 83, 351-353DOI: (10.1038/ki.2012.437) Copyright © 2013 International Society of Nephrology Terms and Conditions