Fanelli, G;
Gonzalez-Cordero, A;
Gardner, PJ;
Peng, Q;
Fernando, M;
Kloc, M;
Farrar, CA;
... Sacks, SH; + view all
(2017)
Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress.
Scientific Reports
, 7
, Article 14625. 10.1038/s41598-017-15212-z.
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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.
| Type: | Article |
|---|---|
| Title: | Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41598-017-15212-z |
| Publisher version: | http://dx.doi.org/10.1038/s41598-017-15212-z |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| Keywords: | Cell death and immune response, Complement cascade |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10033928 |
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