The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings.
The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings.
复制标题
DOI：
10.1038/jid.2012.194
复制
发表时间：
2013-01
影响因子：
6.5
通讯作者：
Russell, Chris B.
中科院分区：
文献类型：
--
作者：
Martin, David A.;Towne, Jennifer E.;Kricorian, Gregory;Klekotka, Paul;Gudjonsson, Johann E.;Krueger, James G.;Russell, Chris B.
虽然银屑病的组织学变化早已被很好地表征，但其潜在的细胞和分子机制在过去20年才开始被阐明。促炎因子如肿瘤坏死因子(TNF)-α在银屑病发病中起核心作用，许多T辅助1 （Th1）细胞因子和信使rna在银屑病病变中升高。白细胞介素- 17a （IL-17A）、IL-17F和其他Th17细胞衍生的细胞因子已在小鼠模型中显示可诱导模拟人类牛皮癣的特征。本文综述了银屑病中IL-17细胞因子家族的生物学研究进展，以及从动物模型和人类临床研究中获得的分子和遗传信息，证实IL-17是银屑病中重要的促炎细胞因子。银屑病病变中IL-17A、IL-17C和IL-17F的表达显著增加，成功的治疗与多种基因（包括IL-17下游的效应分子，如细胞因子、趋化因子和抗菌肽）的表达恢复到接近正常水平有关。本文讨论了正在开发的靶向IL-17的治疗药物，并提出了IL-17在牛皮癣发病机制中的关键作用的新模型。
Although the histologic changes seen in psoriasis have long been well characterized, the underlying cellular and molecular mechanisms have only begun to be elucidated over the past 20 years. Proinflammatory factors such as tumor necrosis factor (TNF)-α have a central role in psoriasis pathogenesis, and many T helper 1 (Th1) cytokines and messenger RNAs are elevated in psoriatic lesions. Interleukin-17A (IL-17A), IL-17F, and other Th17 cell–derived cytokines have been shown in murine models to induce features that mimic human psoriasis. This review focuses on the emerging biology of the IL-17 cytokine family in psoriasis, and on the molecular and genetic information gained from animal models and human clinical studies that confirm IL-17 as a crucial proinflammatory cytokine in psoriasis. Expression of IL-17A, IL-17C, and IL-17F is strikingly increased in psoriatic lesions, and successful therapy is associated with restoration of the expression of a wide range of genes (including effector molecules downstream of IL-17 such as cytokines, chemokines, and antimicrobial peptides) to near normal levels. Therapeutic agents in development that target IL-17 are discussed, and an emerging model of the key role of IL-17 in the pathogenesis of psoriasis is presented.
登录
查看更多内容
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
64.8
作者：
Bettelli, E;Carrier, YJ;Kuchroo, VK
通讯作者：
Kuchroo, VK
影响因子：
4.4
作者：
Claudio, Estefania;Sonder, Soren Ulrik;Saret, Sun;Carvalho, Gabrielle;Ramalingam, Thirumalai R.;Wynn, Thomas A.;Chariot, Alain;Garcia-Perganeda, Antonio;Leonardi, Antonio;Paun, Andrea;Chen, Amy;Ren, Nina Y.;Wang, Hongshan;Siebenlist, Ulrich
通讯作者：
Siebenlist, Ulrich
影响因子：
168.9
作者：
Chaudhari, U;Romano, P;Gottlieb, AB
通讯作者：
Gottlieb, AB
影响因子：
30.8
作者：
Fisher, Sheila A.;Tremelling, Mark;Anderson, Carl A.;Gwilliam, Rhian;Bumpstead, Suzannah;Prescott, Natalie J.;Nimmo, Elaine R.;Massey, Dunecan;Berzuini, Carlo;Johnson, Christopher;Barrett, Jeffrey C.;Cummings, Fraser R.;Drummond, Hazel;Lees, Charlie W.;Onnie, Clive M.;Hanson, Catherine E.;Blaszczyk, Katarzyna;Inouye, Mike;Ewels, Philip;Ravindrarajah, Radhi;Keniry, Andrew;Hunt, Sarah;Carter, Martyn;Watkins, Nick;Ouwehand, Willem;Lewis, Cathryn M.;Cardon, Lon;Lobo, Alan;Forbes, Alastair;Sanderson, Jeremy;Jewell, Derek P.;Mansfield, John C.;Deloukas, Panos;Mathew, Christopher G.;Parkes, Miles;Satsangi, Jack
通讯作者：
Satsangi, Jack