Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress.
Human stem cell-derived retinal epithelial cells activate complement via collectin 11 in response to stress.
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DOI：
10.1038/s41598-017-15212-z
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发表时间：
2017-11-07
影响因子：
4.6
通讯作者：
Sacks SH
中科院分区：
文献类型：
--
作者：
Fanelli G;Gonzalez-Cordero A;Gardner PJ;Peng Q;Fernando M;Kloc M;Farrar CA;Naeem A;Garred P;Ali RR;Sacks SH
视网膜相关性黄斑变性（AMD）是失明的主要原因，并且与补体失调有关。这种疾病是干细胞治疗的潜在目标，但成功可能受到炎症反应的限制。我们研究了人诱导多能干细胞（iPSC）衍生的RPE细胞的先天免疫特性，特别是关于补体途径。我们专注于collectin-11（CL-11），这是一种模式识别分子，可以触发肾上皮组织中的补体激活。我们发现了CL-11在iPS-RPE细胞和细胞外液中的组成性和缺氧诱导表达的证据。细胞表面上的补体活化与CL-11结合一起发生。CL-11已显示通过识别L-岩藻糖激活炎症反应，我们通过显示岩藻糖苷酶处理的细胞在很大程度上未能激活补体来证实这一点。CL-11在健康鼠和人视网膜组织中的存在证实了CL-11的生物学相关性。我们的数据描述了一种新的补体激活触发机制，这在疾病发病机制和治疗干预中可能是重要的。
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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活化的蛋白 C 可将视网膜从缺血引起的细胞死亡中拯救出来。
影响因子：
4.4
作者：
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通讯作者：
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影响因子：
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作者：
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影响因子：
56.9
作者：
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通讯作者：
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