Lupus Skin Is Primed for IL-6 Inflammatory Responses through a Keratinocyte-Mediated Autocrine Type I Interferon Loop.
Lupus Skin Is Primed for IL-6 Inflammatory Responses through a Keratinocyte-Mediated Autocrine Type I Interferon Loop.
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DOI：
10.1016/j.jid.2016.09.008
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发表时间：
2017-01
期刊：
影响因子：
--
通讯作者：
Kahlenberg JM
中科院分区：
文献类型：
--
作者：
Stannard JN;Reed TJ;Myers E;Lowe L;Sarkar MK;Xing X;Gudjonsson JE;Kahlenberg JM
皮肤红斑狼疮（CLE）是一种毁容和常见的表现，在系统性红斑狼疮（SLE），这种倾向的皮肤炎症的病因是未知的。在这里，我们试图检查角质形成细胞作为IL-6的一个重要来源，并确定其在CLE生产增加的机制。通过实时PCR和免疫组化，与对照组相比，盘状和亚急性皮肤红斑狼疮病变的评估显示表皮IL-6显著上调。与健康对照组相比，暴露于TLR 2、3或4激动剂或暴露于UVB辐射后，狼疮患者未受影响皮肤的角质形成细胞产生显著更多的IL-6。重要的是，用I型干扰素（IFNα和IFNκ）预处理增加了对照角质形成细胞的IL-6产生，并且I型IFN阻断剂降低了狼疮角质形成细胞的IL-6分泌。TLR 2和UVB处理后狼疮角质形成细胞分泌的角质形成细胞特异性IFNκ显著增加，IFNκ的中和作用降低了狼疮角质形成细胞产生的IL-6。因此，狼疮角质形成细胞以I型IFN依赖性方式引发IL-6过度产生。狼疮角质形成细胞产生的IFNκ增加驱动了这种反应，表明IFNκ可能在CLE中起致病作用，并可作为治疗的新靶点。
Cutaneous lupus erythematosus (CLE) is a disfiguring and common manifestation in systemic lupus erythematosus (SLE), and the etiology of this predisposition for cutaneous inflammation is unknown. Here, we sought to examine the keratinocyte as an important source of IL-6 and define the mechanism for its increased production in CLE. Evaluation of discoid and subacute cutaneous lupus erythematosus lesions revealed significant epidermal upregulation of IL-6 when compared with control via real-time PCR and immunohistochemistry. Keratinocytes from unaffected skin of lupus patients produced significantly more IL-6 compared with healthy controls following exposure to TLR2, 3, or 4 agonists, or exposure to UVB radiation. Importantly, pretreatment with type I interferons (IFNα and IFNκ) increased IL-6 production by control keratinocytes, and type I IFN blockade decreased IL-6 secretion by lupus keratinocytes. Secretion of keratinocyte-specific IFNκ was significantly increased after TLR2 and UVB treatment in lupus keratinocytes and neutralization of IFNκ decreased IL-6 production by lupus keratinocytes. Thus, lupus keratinocytes are primed for IL-6 hyper-production in a type I IFN-dependent manner. Increased production of IFNκ by lupus keratinocytes drives this response, indicating that IFNκ may play a pathogenic role in CLE and serve as a novel target for treatment.
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DOI：
10.1084/jem.172.6.1609
发表时间：
1990-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Köck A;Schwarz T;Kirnbauer R;Urbanski A;Perry P;Ansel JC;Luger TA
通讯作者：
Luger TA
影响因子：
4.8
作者：
LaFleur, DW;Nardelli, B;Moore, PA
通讯作者：
Moore, PA
影响因子：
2.7
作者：
Kadowaki, N;Liu, YJ
通讯作者：
Liu, YJ
影响因子：
9.1
作者：
Chun, Hye-Young;Chung, Jae-Wook;Suh, Chang-Hee
通讯作者：
Suh, Chang-Hee
影响因子：
3.4
作者：
Makol, Ashima;Gibson, Lawrence E.;Michet, Clement J.
通讯作者：
Michet, Clement J.