Collectin-11 detects stress-induced L-fucose pattern to trigger renal epithelial injury

J Clin Invest. 2016 May 2;126(5):1911-25. doi: 10.1172/JCI83000. Epub 2016 Apr 18.


Physiochemical stress induces tissue injury as a result of the detection of abnormal molecular patterns by sensory molecules of the innate immune system. Here, we have described how the recently discovered C-type lectin collectin-11 (CL-11, also known as CL-K1 and encoded by COLEC11) recognizes an abnormal pattern of L-fucose on postischemic renal tubule cells and activates a destructive inflammatory response. We found that intrarenal expression of CL-11 rapidly increases in the postischemic period and colocalizes with complement deposited along the basolateral surface of the proximal renal tubule in association with L-fucose, the potential binding ligand for CL-11. Mice with either generalized or kidney-specific deficiency of CL-11 were strongly protected against loss of renal function and tubule injury due to reduced complement deposition. Ex vivo renal tubule cells showed a marked capacity for CL-11 binding that was induced by cell stress under hypoxic or hypothermic conditions and prevented by specific removal of L-fucose. Further analysis revealed that cell-bound CL-11 required the lectin complement pathway-associated protease MASP-2 to trigger complement deposition. Given these results, we conclude that lectin complement pathway activation triggered by ligand-CL-11 interaction in postischemic tissue is a potent source of acute kidney injury and is amenable to sugar-specific blockade.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / genetics
  • Acute Kidney Injury / metabolism*
  • Acute Kidney Injury / pathology
  • Animals
  • Collectins / genetics
  • Collectins / metabolism*
  • Complement Pathway, Mannose-Binding Lectin / drug effects*
  • Complement Pathway, Mannose-Binding Lectin / genetics
  • Complement System Proteins / genetics
  • Complement System Proteins / metabolism*
  • Fucose / toxicity*
  • Kidney Tubules, Proximal / injuries*
  • Kidney Tubules, Proximal / metabolism*
  • Kidney Tubules, Proximal / pathology
  • Mannose-Binding Protein-Associated Serine Proteases / genetics
  • Mannose-Binding Protein-Associated Serine Proteases / metabolism
  • Mice
  • Mice, Knockout


  • Collectins
  • Fucose
  • Complement System Proteins
  • MASP-2 protein, mouse
  • Mannose-Binding Protein-Associated Serine Proteases