C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita.
C-type lectin receptor expression is a hallmark of neutrophils infiltrating the skin in epidermolysis bullosa acquisita.
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DOI：
10.3389/fimmu.2023.1266359
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发表时间：
2023
影响因子：
7.3
通讯作者：
Amber, Kyle T.
中科院分区：
文献类型：
--
作者：
Guerrero-Juarez, Christian F.;Schilf, Paul;Li, Jing;Zappia, Maria Paula;Bao, Lei;Patel, Payal M.;Gieseler-Tillmann, Jenny;Murthy, Sripriya;Cole, Connor;Sverdlov, Maria;Frolov, Maxim V.;Hashimoto, Takashi;Ishii, Norito;Ruelicke, Thomas;Bieber, Katja;Ludwig, Ralf J.;Sadik, Christian D.;Amber, Kyle T.
关键词：
炎性获得性大疱性表皮病（EBA）的特征在于对抗VII型胶原（COL 7）抗体的嗜酸性反应，导致皮肤炎症和水疱的发生。EBA的抗体转移模型密切反映了这种EBA表型。为了更好地理解EBA中从外周血募集到病变皮肤中时在中性粒细胞中诱导的变化，我们对全血和皮肤解离物进行单细胞RNA测序，以捕获最小扰动的中性粒细胞并表征其转录组。通过这种方法，我们确定了循环活化中性粒细胞和皮内中性粒细胞之间的明显区别。最引人注目的是，多种C型凝集素受体的基因表达明显失调，此前曾有报道称这些受体可以协调宿主防御真菌和选定细菌。在证实实验性EBA以及炎症性EBA患者的病变皮肤中Clec 4 n、Clec 4d和Clec 4 e的上调后，我们在全面缺陷的Clec 4 e −/−和Clec 4d −/−小鼠以及嗜中性粒细胞特异性Clec 4 n −/−小鼠中进行了功能研究。在EBA模型中，这些基因的缺陷并没有减少疾病。总的来说，我们的研究结果表明，虽然Clec 4 n，Clec 4d和Clec 4 e的上调是活化的真皮中性粒细胞群体的标志，但它们对EBA发病机制的单独贡献是微不足道的。
Inflammatory epidermolysis bullosa acquisita (EBA) is characterized by a neutrophilic response to anti-type VII collagen (COL7) antibodies resulting in the development of skin inflammation and blistering. The antibody transfer model of EBA closely mirrors this EBA phenotype. To better understand the changes induced in neutrophils upon recruitment from peripheral blood into lesional skin in EBA, we performed single-cell RNA-sequencing of whole blood and skin dissociate to capture minimally perturbed neutrophils and characterize their transcriptome. Through this approach, we identified clear distinctions between circulating activated neutrophils and intradermal neutrophils. Most strikingly, the gene expression of multiple C-type lectin receptors, which have previously been reported to orchestrate host defense against fungi and select bacteria, were markedly dysregulated. After confirming the upregulation of Clec4n, Clec4d, and Clec4e in experimental EBA as well as in lesional skin from patients with inflammatory EBA, we performed functional studies in globally deficient Clec4e−/− and Clec4d−/− mice as well as in neutrophil-specific Clec4n−/− mice. Deficiency in these genes did not reduce disease in the EBA model. Collectively, our results suggest that while the upregulation of Clec4n, Clec4d, and Clec4e is a hallmark of activated dermal neutrophil populations, their individual contribution to the pathogenesis of EBA is dispensable.
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影响因子：
14.9
作者：
Kuleshov MV;Jones MR;Rouillard AD;Fernandez NF;Duan Q;Wang Z;Koplev S;Jenkins SL;Jagodnik KM;Lachmann A;McDermott MG;Monteiro CD;Gundersen GW;Ma'ayan A
通讯作者：
Ma'ayan A
DOI：
10.1084/jem.20100793
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barrett NA;Rahman OM;Fernandez JM;Parsons MW;Xing W;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
影响因子：
--
作者：
Kasprick, Anika;Bieber, Katja;Ludwig, Ralf J
通讯作者：
Ludwig, Ralf J
影响因子：
3.1
作者：
Loures, Flavio V.;Pina, Adriana;Calich, Vera L. G.
通讯作者：
Calich, Vera L. G.
影响因子：
5.6
作者：
Marchi, L. F.;Sesti-Costa, R.;Mantovani, B.
通讯作者：
Mantovani, B.