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Sci Rep. 2017 Nov 7;7(1):14625. doi: 10.1038/s41598-017-15212-z.

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

Author information

1
MRC Centre for Transplantation, King's College London and Guy's and St Thomas' NHS Trust, Guy's Hospital, London, UK.
2
UCL Institute of Ophthalmology, London, UK.
3
Laboratory of Molecular Medicine, Department of Clinical Immunology Section 7631 Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
4
MRC Centre for Transplantation, King's College London and Guy's and St Thomas' NHS Trust, Guy's Hospital, London, UK. steven.sacks@kcl.ac.uk.

Abstract

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.

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