Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress

Research output: Contribution to journalJournal articleResearchpeer-review

  • Giorgia Fanelli
  • Anai Gonzalez-Cordero
  • Peter J Gardner
  • Qi Peng
  • Milan Fernando
  • Magdalena Kloc
  • Conrad A Farrar
  • Arifa Naeem
  • Garred, Peter
  • Robin R Ali
  • Steven H Sacks

Age-related macular degeneration (AMD) is a major cause of blindness and is associated with complement dysregulation. The disease is a potential target for stem cell therapy but success is likely to be limited by the inflammatory response. We investigated the innate immune properties of human induced-pluripotent stem cell (iPSC)-derived RPE cells, particularly with regard to the complement pathway. We focused on collectin-11 (CL-11), a pattern recognition molecule that can trigger complement activation in renal epithelial tissue. We found evidence of constitutive and hypoxia-induced expression of CL-11 in iPS-RPE cells, and in the extracellular fluid. Complement activation on the cell surface occurred in conjunction with CL-11 binding. CL-11 has been shown to activate inflammatory responses through recognition of L-fucose, which we confirmed by showing that fucosidase-treated cells, largely, failed to activate complement. The presence of CL-11 in healthy murine and human retinal tissues confirmed the biological relevance of CL-11. Our data describe a new trigger mechanism of complement activation that could be important in disease pathogenesis and therapeutic interventions.

Original languageEnglish
Article number14625
JournalScientific Reports
Number of pages13
Publication statusPublished - 2017

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