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

TY - JOUR

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 - 2017/12/1

Y1 - 2017/12/1

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

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

M1 - 14625

ER -