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. / Fanelli, Giorgia; Gonzalez-Cordero, Anai; Gardner, Peter J; Peng, Qi; Fernando, Milan; Kloc, Magdalena; Farrar, Conrad A; Naeem, Arifa; Garred, Peter; Ali, Robin R; Sacks, Steven H.
In: Scientific Reports, Vol. 7, 14625, 2017.Research output: Contribution to journal › Journal article › peer-review
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T1 - Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress
AU - Fanelli, Giorgia
AU - Gonzalez-Cordero, Anai
AU - Gardner, Peter J
AU - Peng, Qi
AU - Fernando, Milan
AU - Kloc, Magdalena
AU - Farrar, Conrad A
AU - Naeem, Arifa
AU - Garred, Peter
AU - Ali, Robin R
AU - Sacks, Steven H
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
U2 - 10.1038/s41598-017-15212-z
DO - 10.1038/s41598-017-15212-z
M3 - Journal article
C2 - 29116192
VL - 7
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 14625
ER -
ID: 196041862