Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression.
Innate Immune Dysfunction in Rosacea Promotes Photosensitivity and Vascular Adhesion Molecule Expression.
复制标题
玫瑰痤疮中的先天性免疫功能障碍会加剧光敏感性并促进血管黏附分子的表达。
DOI：
10.1016/j.jid.2019.08.436
复制
发表时间：
2020-03
影响因子：
6.5
通讯作者：
Gallo, Richard L.
中科院分区：
文献类型：
--
作者：
Kulkarni, Nikhil N.;Takahashi, Toshiya;Sanford, James A.;Tong, Yun;Gombart, Adrian F.;Hinds, Brian;Cheng, Joyce Y.;Gallo, Richard L.
酒渣鼻是一种慢性皮肤病，其特征为光敏感、真皮血管行为异常、炎症以及抗菌肽LL - 37表达增强。我们观察到酒渣鼻患者的真皮内皮细胞中血管细胞黏附分子1（VCAM1）表达增加，并假设LL - 37可能是导致这种反应的原因。消化来自暴露于中波紫外线（UVB）的角质形成细胞的双链RNA（dsRNA），会阻断这些细胞诱导真皮微血管内皮细胞上黏附分子表达的能力。然而，一种合成的非编码小核仁RNA（snoU1RNA）仅在LL - 37存在的情况下，才能增加内皮细胞上的黏附分子，这表明UVB照射促进dsRNA和LL - 37产生的能力，是内皮细胞对角质形成细胞产生反应的原因。对内皮细胞的RNA进行测序，揭示了与人类疾病相关的基因本体论通路的激活，如I型和II型干扰素信号传导、细胞间黏附、白细胞趋化和血管生成。功能相关性表现为dsRNA和LL - 37促进单核细胞黏附并穿过内皮细胞单层迁移。通过基因敲低Toll样受体3（TLR3）、视黄酸诱导基因I（RIGI）或干扰素调节因子1（IRF1），可减少单核细胞与内皮细胞的黏附，证实了dsRNA识别通路的作用。这些观察结果表明，LL - 37的表达如何导致酒渣鼻对UVB辐射的敏感性增强。
Rosacea is a chronic skin disease characterized by photosensitivity, abnormal dermal vascular behavior, inflammation and enhanced expression of the antimicrobial peptide LL-37. We observed that dermal endothelial cells in rosacea had increased expression of VCAM1 and hypothesized that LL-37 could be responsible for this response. Digestion of dsRNA from keratinocytes exposed to ultraviolet B radiation (UVB) blocked the capacity of these cells to induce adhesion molecules on dermal microvascular endothelial cells. However, a synthetic non-coding snoU1RNA was only capable of increasing adhesion molecules on endothelial cells in the presence of LL-37, suggesting that the capacity of UVB exposure to promote both dsRNA and LL-37 was responsible for the endothelial response to keratinocytes. Sequencing of RNA from endothelial cells uncovered activation of gene ontology pathways relevant to the human disease such as type I and II interferon signaling, cell-cell adhesion, leukocyte chemotaxis and angiogenesis. Functional relevance was demonstrated as dsRNA and LL-37 promoted adhesion and transmigration of monocytes across endothelial cell monolayers. Gene knock down of TLR3, RIGI or IRF1 decreased monocyte adhesion endothelial cells, confirming the role of dsRNA recognition pathways. These observations show how expression of LL-37 can lead to enhanced sensitivity to UVB radiation in rosacea.
登录
查看更多内容
影响因子：
4.8
作者：
Kim, I;Moon, SO;Koh, GY
通讯作者：
Koh, GY
影响因子：
64.8
作者：
Alexopoulou, L;Holt, AC;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
64.8
作者：
Nizet, V;Ohtake, T;Gallo, RL
通讯作者：
Gallo, RL
David Gene功能分类工具：一种以生物模块为中心的新型算法，可在功能上分析大基因列表。
影响因子：
12.3
作者：
Huang, Da Wei;Sherman, Brad T;Tan, Qina;Collins, Jack R;Alvord, W Gregory;Roayaei, Jean;Stephens, Robert;Baseler, Michael W;Lane, H Clifford;Lempicki, Richard A
通讯作者：
Lempicki, Richard A
影响因子：
5.6
作者：
D'Orazio J;Jarrett S;Amaro-Ortiz A;Scott T
通讯作者：
Scott T