Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress
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- Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress
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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.
Originalsprog | Engelsk |
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Artikelnummer | 14625 |
Tidsskrift | Scientific Reports |
Vol/bind | 7 |
Antal sider | 13 |
ISSN | 2045-2322 |
DOI | |
Status | Udgivet - 2017 |
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