Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes.
Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active Psoriasis and localized with keratinocytes, dendritic cells and other leukocytes.
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DOI：
10.1111/exd.13378
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发表时间：
2017-11
影响因子：
3.6
通讯作者：
Krueger JG
中科院分区：
文献类型：
--
作者：
Fuentes-Duculan J;Bonifacio KM;Hawkes JE;Kunjravia N;Cueto I;Li X;Gonzalez J;Garcet S;Krueger JG
银屑病是一种常见的免疫介导的疾病，影响北美和欧洲2-4%的个体。在过去的十年中，研究的进展已经导致了对参与银屑病发病机制的免疫途径的更好理解，并刺激了靶向治疗的发展。最近，已经描述了三种银屑病自身抗原：cathelicidin（LL-37），含有血小板反应蛋白1型基序样5（ADAMTSL 5）的去整合素和金属蛋白酶结构域，以及由磷脂酶A2组IVD（PLA 2G 4D）产生的脂质抗原。重要的是要建立这些银屑病自身抗原的表达，调节和治疗调制。在这项研究中，我们对非皮损和皮损银屑病皮肤进行免疫组织化学和双色免疫荧光，以表征ADAMTSL 5和LL-37，以及它们与CD 3 + T细胞，CD 11 c+树突状细胞和CD 163+巨噬细胞的共表达，这些细胞是驱动这种疾病的主要免疫细胞。我们的结果显示，ADAMTSL 5+和LL 37+细胞在病变皮肤中显著增加（p<0.05），并且在真皮中由许多树突状细胞、巨噬细胞和一些T细胞共表达。基因表达分析显示，LL-37在病变皮肤中显著上调（p<0.05），并且在用依那西普治疗后显著下调。IL-17或TNFα阻断也显著减少ADAMTSL 5+和LL 37+细胞，表明疾病相关细胞因子对银屑病自身抗原的前馈诱导。
Psoriasis is a common immune-mediated disease that affects 2–4% of individuals in North America and Europe. In the past decade, advances in research have led to an improved understanding of immune pathways involved in the pathogenesis of psoriasis and has spurred the development of targeted therapeutics. Recently, three psoriasis autoantigens have been described: cathelicidin (LL-37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5 (ADAMTSL5), and lipid antigens generated by phospholipase A2 group IVD (PLA2G4D). It is important to establish the expression, regulation, and therapeutic modulation of these psoriasis autoantigens. In this study, we performed immunohistochemistry and two-color immunofluorescence on non-lesional and lesional psoriasis skin to characterize ADAMTSL5 and LL-37, and their co-expression with CD3+ T-cells, CD11c+ dendritic cells, and CD163+ macrophages, which are the main immune cells that drive this disease. Our results showed that ADAMTSL5+ and LL37+ cells are significantly (p<0.05) increased in lesional skin and are co-expressed by many dendritic cells, macrophages, and some T-cells in the dermis. Gene expression analysis showed significant (p<0.05) upregulation of LL-37 in lesional skin and significant downregulation following treatment with etanercept. ADAMTSL5+ and LL37+ cells are also significantly decreased by IL-17 or TNFα blockade, suggesting feed-forward induction of psoriasis autoantigens by disease-related cytokines.
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DOI：
10.1084/jem.21213insight3
发表时间：
2015-12-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Krueger JG
通讯作者：
Krueger JG
影响因子：
6.5
作者：
Morizane, Shin;Yamasaki, Kenshi;Muehleisen, Beda;Kotol, Paul F.;Murakami, Masamoto;Aoyama, Yumi;Iwatsuki, Keiji;Hata, Tissa;Gallo, Richard L.
通讯作者：
Gallo, Richard L.
影响因子：
4.8
作者：
Chiba, H;Michibata, H;Imai, Y
通讯作者：
Imai, Y
影响因子：
--
作者：
GUBNER, R
通讯作者：
GUBNER, R
影响因子：
30.5
作者：
通讯作者：
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