Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes.
Synergistic induction of IL-23 by TNFα, IL-17A, and EGF in keratinocytes.
复制标题
角质形成细胞中TNFα，IL-17A和EGF对IL-23的协同诱导。
DOI：
10.1016/j.cyto.2020.155357
复制
发表时间：
2021-03
期刊：
影响因子：
3.8
通讯作者：
Liu Y
中科院分区：
文献类型：
--
作者：
Ehst B;Wang Z;Leitenberger J;McClanahan D;De La Torre R;Sawka E;Ortega-Loayza AG;Strunck J;Greiling T;Simpson E;Liu Y
IL-23是一种炎性细胞因子，其通过增强Th 17细胞增殖和存活以及Th 17细胞因子产生而在Th 17免疫中起重要作用。IL-23在包括银屑病在内的Th 17介导的炎性疾病的发展中具有致病作用。尽管通过阻断IL-23成功治疗银屑病，但银屑病患者中IL-23表达的调节在很大程度上是未知的。树突状细胞通常被认为是银屑病中IL-23的主要来源。虽然在银屑病表皮中发现了高水平的IL-23，但在银屑病角化病中IL-23的表达仍然是一个有争议的问题。在这项研究中，我们证明了IL-23的产生是由TNFα和IL-17 A在人角质形成细胞中的组合诱导的。此外，TNFα和IL-17 A对IL-23的诱导作用在银屑病角质形成细胞中进一步增加，并通过EGFR信号传导增强。尽管树突状细胞和巨噬细胞中的toll样受体激动剂也能强烈诱导IL-23，但这些细胞类型中的IL-23表达不受TNFα、IL-17 A和EGFR信号转导的调节。鉴于IL-23对维持Th 17活化至关重要，角质形成细胞中TNFα、IL-17 A和EGF诱导的IL-23可能在银屑病发病机制以及EGFR抑制治疗相关皮疹中发挥重要病理作用。
IL-23 is an inflammatory cytokine that plays an essential role in Th17 immunity by enhancing Th17 cell proliferation and survival, and Th17 cytokine production. IL-23 has pathogenic roles in the development of Th17-mediated inflammatory diseases including psoriasis. Despite successful treatment of psoriasis by blocking IL-23, the regulation of IL-23 expression in psoriasis patients is largely unknown. Dendritic cells are generally considered to be the primary source of IL-23 in psoriasis. While high levels of IL-23 are found in psoriatic epidermis, IL-23 expression in psoriatic keratinoctyes remains a controversial issue. In this study, we demonstrated that IL-23 production is induced by a combination of TNFα and IL-17A in human keratinocytes. Additionally, this IL-23 induction by TNFα and IL-17A is further increased in psoriatic keratinocytes and is enhanced by EGFR signaling. Although IL-23 is also robustly induced by toll-like receptor agonists in dendritic cells and macrophages, IL-23 expression in these cell types is not regulated by TNFα, IL-17A, and EGFR signaling. Given that IL-23 is essential for maintaining Th17 activation, IL-23 induction by TNFα, IL-17A, and EGF in keratinocytes could play an important pathological role in psoriasis pathogenesis as well as the cutaneous rash associated with EGFR inhibition therapy.
登录
查看更多内容
影响因子：
32.4
作者：
Oppmann, B;Lesley, R;Kastelein, RA
通讯作者：
Kastelein, RA
影响因子：
30.8
作者：
Nair RP;Duffin KC;Helms C;Ding J;Stuart PE;Goldgar D;Gudjonsson JE;Li Y;Tejasvi T;Feng BJ;Ruether A;Schreiber S;Weichenthal M;Gladman D;Rahman P;Schrodi SJ;Prahalad S;Guthery SL;Fischer J;Liao W;Kwok PY;Menter A;Lathrop GM;Wise CA;Begovich AB;Voorhees JJ;Elder JT;Krueger GG;Bowcock AM;Abecasis GR;Collaborative Association Study of Psoriasis
通讯作者：
Collaborative Association Study of Psoriasis
白细胞介素 17 受体 A 调节体内单核细胞亚群和巨噬细胞的生成。
影响因子：
3.7
作者：
Ge S;Hertel B;Susnik N;Rong S;Dittrich AM;Schmitt R;Haller H;von Vietinghoff S
通讯作者：
von Vietinghoff S
影响因子：
14.8
作者：
Aasen, Trond;Izpisua Belmonte, Juan Carlos
通讯作者：
Izpisua Belmonte, Juan Carlos
DOI：
10.4049/jimmunol.1800013
发表时间：
2018-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Hawkes JE;Yan BY;Chan TC;Krueger JG
通讯作者：
Krueger JG