Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen.
Filaggrin-deficient mice exhibit TH17-dominated skin inflammation and permissiveness to epicutaneous sensitization with protein antigen.
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DOI：
10.1016/j.jaci.2009.05.042
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发表时间：
2009-09
影响因子：
14.2
通讯作者：
Geha, Raif S.
中科院分区：
文献类型：
--
作者：
Oyoshi, Michiko K.;Murphy, George F.;Geha, Raif S.
微丝蛋白对皮肤屏障功能很重要，在15%-20%的特应性皮炎患者中会发生突变。检查微丝蛋白缺乏是否易导致皮肤炎症和皮肤上皮(EC)对蛋白质抗原的致敏。用H&E染色和免疫组织化学方法检测微丝蛋白缺陷ft/ft小鼠和WT对照小鼠的皮肤组织学变化。定量RT-PCR检测细胞因子mRNA的表达。用双抗体夹心法检测小鼠血清抗体水平和脾细胞分泌细胞因子。FT/ft小鼠在28周龄后出现湿疹皮损，血清IgE和IgG1水平逐渐升高。8周龄ft/ft小鼠正常皮肤表皮增厚，真皮中CD_4~+细胞浸润增多，IL-17、IL-6和IL-23mRNA表达增加，而IL-4、IL-13和干扰素-γ无表达。32周龄的ft/ft小鼠的皮损皮肤表现出定性上相似的变化，但更明显的变化，并升高了IL-4mRNA水平。8周龄ft/ft小鼠皮下注射卵清蛋白后，表皮增厚，真皮由CD_4~+细胞向真皮渗透，但未见嗜酸性粒细胞，IL-17、IL-6、IL-23、IL-4和干扰素-γ的表达增加，而IL-5和IL-13的表达无明显变化。EC致敏的ft/ft小鼠的脾细胞在OVA刺激下分泌细胞因子，它们的血清中含有OVA特异性的IgE和IgG1抗体。微丝蛋白缺陷小鼠表现出以Th17为主的皮肤炎症，随着年龄的增长出现湿疹变化，并允许EC用蛋白质抗原致敏。
Filaggrin is important for skin barrier function and is mutated in 15-20% of patients with atopic dermatitis. To examine whether filaggrin deficiency predisposes to skin inflammation and epicutaneous (EC) sensitization with protein antigen. Skin histology in filaggrin-deficient ft/ft mice and WT controls was assessed by H&E staining and immunohistochemistry. Cytokine mRNA expression was examined by quantitative RT-PCR. Serum antibody levels and splenocyte secretion of cytokines were measured by ELISA. ft/ft mice developed eczematous skin lesions after age 28 weeks and a progressive increase in serum IgE and IgG1 levels. Normal appearing skin from 8-week-old ft/ft mice had epidermal thickening and increased dermal infiltration with CD4+ cells and expression of mRNA for IL-17, IL-6 and IL-23, but not IL-4, IL-13 or IFN-γ. Lesional skin of 32-week-old ft/ft mice exhibited qualitatively similar, but more pronounced, changes, and elevated IL-4 mRNA levels. EC application of ovalbumin (OVA) to shaved skin of 8-week-old ft/ft mice, but not WT mice, resulted in increased epidermal thickening, dermal infiltration by CD4+ cells, but not eosinophils, and expression of IL-17, IL-6, IL-23, IL-4 and IFN-γ, but not IL-5 or IL-13, mRNA. Splenocytes from EC sensitized ft/ft mice, but not controls, secreted cytokines in response to OVA stimulation and their sera, but not those of controls, contained OVA specific IgE and IgG1 antibodies. Filaggrin deficient mice exhibit Th17-dominated skin inflammation, eczematous changes with age, and are permissive to EC sensitization with protein antigen.
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影响因子：
14.2
作者：
Larsen, Jeppe Madura;Bonefeld, Charlotte Menne;Skov, Lone
通讯作者：
Skov, Lone
影响因子：
56.9
作者：
SNAPPER, CM;PAUL, WE
通讯作者：
PAUL, WE
影响因子：
3.2
作者：
Makino, T;Takaishi, M;Huh, NH
通讯作者：
Huh, NH
DOI：
10.1084/jem.20061401
发表时间：
2006-11-27
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Schnyder-Candrian S;Togbe D;Couillin I;Mercier I;Brombacher F;Quesniaux V;Fossiez F;Ryffel B;Schnyder B
通讯作者：
Schnyder B
影响因子：
3.1
作者：
LANE, PW
通讯作者：
LANE, PW