Innate immune cell-produced IL-17 sustains inflammation in bullous pemphigoid.
Innate immune cell-produced IL-17 sustains inflammation in bullous pemphigoid.
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DOI：
10.1038/jid.2014.263
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发表时间：
2014-12
影响因子：
6.5
通讯作者：
Antonicelli, Frank
中科院分区：
文献类型：
--
作者：
Le Jan, Sebastien;Plee, Julie;Vallerand, David;Dupont, Aurelie;Delanez, Elodie;Durlach, Anne;Jackson, Patricia L.;Blalock, J. Edwin;Bernard, Philippe;Antonicelli, Frank
大疱性类天疱疮（BP）是一种自身免疫性皮肤病，其特征是自身抗体与半桥粒结构的组分结合，导致炎症反应和表皮下水疱形成。为了研究免疫定向在与疾病进展相关的炎症过程中的作用，从31名连续的BP患者中收集水疱液、血清和活检标本。BP患者疱液中IL-6、IL-17、IL-22、IL-23水平升高，血清中TGF-β水平升高。然而，无论是IL-17产生的PBMC的转分化模型上的免疫细胞化学，也不BP活检标本的免疫组化可以证明Th 17淋巴细胞的存在。相反，先天免疫细胞，特别是中性粒细胞，在皮肤病变部位产生IL-17。值得注意的是，超强效局部皮质类固醇应用迅速和显着降低IL-17表达和BP的临床体征。因此，IL-17上调MMP-9和中性粒细胞弹性蛋白酶的表达，这两种蛋白酶参与水疱形成，从而进一步证明其在BP进展中的作用。最后，IL-17诱导的基质降解源于中性粒细胞活化，启动了炎症反应放大环的形成，这可能代表导致维持甚至疾病程度的潜在现象。因此，我们的研究结果可能为BP患者开辟新的治疗策略。
Bullous pemphigoid (BP) is an autoimmune skin disease characterized by the binding of autoantibodies to components of the hemidesmosome structure resulting in an inflammatory response and subepidermal blister formation. To investigate the role of immune orientation in the inflammatory processes associated to disease progression, blister fluid, serum and biopsy specimens were collected from thirty one consecutive BP patients. Blister fluids displayed high level of IL-6, IL-17, IL-22, IL-23, whereas TGF-β was increased in BP sera. However neither immunocytochemistry on a trans-differentiation model of IL-17-producing PBMCs nor immunohistochemistry on BP biopsy specimens could demonstrate the presence of Th17 lymphocytes. Instead innate immune cells, especially neutrophils, produced IL-17 at the skin lesional site. Of note, superpotent topical corticosteroid application quickly and dramatically reduced both IL-17 expression and clinical signs of BP. Consistently, IL-17 upregulated MMP-9 and neutrophil elastase expression, two proteases involved in blister formation, thereof further demonstrating its role in the progress of BP. Finally IL-17-induced matrix degradation originated from neutrophil activation, initiated the formation of an amplification loop of the inflammatory response that could represent the underlying phenomenon leading to the maintenance and even disease extent. Thus, our results could open new therapeutic strategies for BP patients.
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影响因子：
3.7
作者：
Katayama M;Ohmura K;Yukawa N;Terao C;Hashimoto M;Yoshifuji H;Kawabata D;Fujii T;Iwakura Y;Mimori T
通讯作者：
Mimori T
DOI：
10.4049/jimmunol.1100123
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lin AM;Rubin CJ;Khandpur R;Wang JY;Riblett M;Yalavarthi S;Villanueva EC;Shah P;Kaplan MJ;Bruce AT
通讯作者：
Bruce AT
影响因子：
30.5
作者：
Doreau, Agnes;Belot, Alexandre;Bonnefoy-Berard, Nathalie
通讯作者：
Bonnefoy-Berard, Nathalie
影响因子：
4.4
作者：
Hirose, Misa;Recke, Andreas;Ludwig, Ralf J.
通讯作者：
Ludwig, Ralf J.
影响因子：
6.5
作者：
Joly, Pascal;Roujeau, Jean-Claude;Bernard, Philippe
通讯作者：
Bernard, Philippe