Imiquimod Treatment Causes Systemic Disease in Mice Resembling Generalized Pustular Psoriasis in an IL-1 and IL-36 Dependent Manner.
Imiquimod Treatment Causes Systemic Disease in Mice Resembling Generalized Pustular Psoriasis in an IL-1 and IL-36 Dependent Manner.
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DOI：
10.1155/2016/6756138
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发表时间：
2016
影响因子：
4.6
通讯作者：
Jensen LE
中科院分区：
文献类型：
--
作者：
Alvarez P;Jensen LE
泛发性脓疱性银屑病(GPP)是一种严重的银屑病，可由白介素36(IL-36)受体拮抗剂的错义突变引起。除了富含中性粒细胞的皮肤炎症外，GPP患者通常还会出现厌食、发烧、不适和疼痛。咪喹莫特诱导的小鼠皮肤炎症模型已迅速成为研究斑块型银屑病的流行方法，这种银屑病通常不涉及系统性疾病的症状。在该模型中，中性粒细胞向皮肤的募集依赖于炎症介质IL-1，通过其受体IL-1R1和IL-36α。出乎意料的是，我们观察到老鼠也表现出厌食症(体重减轻和食物摄入量减少)、全身不适(活动减少和对筑巢失去兴趣)和疼痛(鼻子鼓起和驼背姿势)的迹象。开发了一种评分系统，允许对测试组进行定量比较。研究发现，雌性小鼠比雄性小鼠患上更严重的疾病。此外，同时缺乏IL-1R1和IL-36α的小鼠几乎没有疾病，而缺乏这两种炎症介质之一的小鼠的疾病没有野生型小鼠那么严重。因此，咪喹莫特诱导的皮肤炎症小鼠模型不仅概括了斑块型牛皮癣，还概括了更严重的症状，即GPP中出现的厌食、不适和疼痛。
Generalized pustular psoriasis (GPP) is a severe form of psoriasis that can be caused by missense mutations in the interleukin-36 (IL-36) receptor antagonist. In addition to neutrophil rich skin inflammation, GPP patients typically also experience anorexia, fever, malaise, and pain. The imiquimod-induced skin inflammation mouse model has rapidly become a popular way to study plaque psoriasis, which typically does not involve symptoms of systemic disease. In this model, neutrophil recruitment to the skin is dependent upon the inflammatory mediators IL-1, via its receptor IL-1R1, and IL-36α. Unexpectedly, we observed that mice also exhibited signs of anorexia (weight loss and decreased food intake), general malaise (decreased activity and loss of interest in building nests), and pain (nose bulging and hunched posture). A scoring system allowing quantitative comparisons of test groups was developed. Female mice were found to develop more severe disease than male mice. Furthermore, mice deficient in both IL-1R1 and IL-36α are nearly disease-free, while mice lacking only one of these inflammatory mediators have less severe disease than wild type mice. Hence, the imiquimod-induced skin inflammation mouse model recapitulates not only plaque psoriasis, but also the more severe symptoms, that is, anorexia, malaise, and pain, seen in GPP.
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DOI：
10.4049/jimmunol.1301481
发表时间：
2014-06-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Foster AM;Baliwag J;Chen CS;Guzman AM;Stoll SW;Gudjonsson JE;Ward NL;Johnston A
通讯作者：
Johnston A
影响因子：
5.4
作者：
Stelzner, Kristin;Herbert, Diana;Saalbach, Anja
通讯作者：
Saalbach, Anja
影响因子：
0.9
作者：
Tominaga C;Yamamoto M;Imai Y;Yamanishi K
通讯作者：
Yamanishi K
影响因子：
9.3
作者：
Bozoyan L;Dumas A;Patenaude A;Vallières L
通讯作者：
Vallières L
影响因子：
6.5
作者：
Uribe-Herranz, Mireia;Lian, Li-Hua;Hooper, Kirsten M.;Milora, Katelynn A.;Jensen, Liselotte E.
通讯作者：
Jensen, Liselotte E.