Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities.
Nonlesional atopic dermatitis skin is characterized by broad terminal differentiation defects and variable immune abnormalities.
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DOI：
10.1016/j.jaci.2010.12.1124
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
Guttman-Yassky E
中科院分区：
文献类型：
--
作者：
Suárez-Fariñas M;Tintle SJ;Shemer A;Chiricozzi A;Nograles K;Cardinale I;Duan S;Bowcock AM;Krueger JG;Guttman-Yassky E
特应性皮炎 (AD) 是一种常见的炎症性皮肤病，具有 Th2 和“T22”免疫极性。尽管最近的数据显示一些患者存在表皮屏障缺陷的遗传倾向，但关于屏障异常与免疫反应在引发疾病中的作用仍然存在基本争论。为了探索 AD 患者是否存在屏障异常和/或背景免疫激活的内在倾向，有必要对非病变 AD (ANL) 皮肤进行广泛研究。通过确定代表病变 AD (AL) 的表皮分化和免疫异常是否也反映在 ANL 皮肤中来表征 ANL 皮肤。我们对 ANL 和 AL 皮肤病变（各 n=12）与正常人类皮肤（n=10）进行了基因组和组织学分析。我们发现 ANL 在终末分化和一些免疫异常方面与正常皮肤明显不同，并且 T 细胞在皮肤中扩张。我们还表明，ANL 皮肤具有可变的免疫表型，这在很大程度上取决于疾病的范围和严重程度。尽管受累和未受累 AD 皮肤之间广泛的终末分化异常在很大程度上相似，这可能是“背景皮肤表型”的原因，但免疫相关基因表达的增加是 AL 和 ANL 皮肤之间最明显的差异之一，可能反映了“临床疾病表型”。我们的研究表明，全身免疫激活可能在正常表皮表型的改变中发挥作用，ANL 皮肤中免疫基因的表达与疾病严重程度指数的高度相关性表明了这一点。
Atopic dermatitis (AD) is a common inflammatory skin disease with a Th2 and “T22” immune polarity. Despite recent data showing a genetic predisposition to epidermal barrier defects in some patients, a fundamental debate still exists regarding the role of barrier abnormalities versus immune responses in initiating the disease. In order to explore whether there is an intrinsic predisposition to barrier abnormalities and/or background immune activation in AD patients an extensive study of non-lesional AD (ANL) skin is necessary. To characterize ANL skin by determining whether epidermal differentiation and immune abnormalities that characterize lesional AD (AL) are also reflected in ANL skin. We performed genomic and histologic profiling of both ANL and AL skin lesions (n=12 each), compared to normal human skin (n=10). We found that ANL is clearly distinct from normal skin with respect to terminal differentiation and some immune abnormalities, and it has a cutaneous expansion of T-cells. We also showed that ANL skin has a variable immune phenotype, which is largely determined by disease extent and severity. Whereas broad terminal differentiation abnormalities were largely similar between involved and uninvolved AD skin, perhaps accounting for the “background skin phenotype,” increased expression of immune-related genes was among the most obvious differences between AL and ANL skin, potentially reflecting the “clinical disease phenotype.” Our study implies that systemic immune activation may play a role in alteration of the normal epidermal phenotype, as suggested by the high correlation in expression of immune genes in ANL skin with disease severity index.
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影响因子：
8.6
作者：
Kim, Byung Eui;Leung, Donald Y. M.;Howell, Michael D.
通讯作者：
Howell, Michael D.
影响因子：
6.5
作者：
Howell, Michael D.;Fairchild, Heather R.;Leung, Donald Y. M.
通讯作者：
Leung, Donald Y. M.
影响因子：
3.6
作者：
Ebert, LA;Schaerli, P;Moser, B
通讯作者：
Moser, B
DOI：
10.1073/pnas.0409569102
发表时间：
2005-02-08
影响因子：
11.1
作者：
Chamian, F;Lowes, MA;Krueger, JG
通讯作者：
Krueger, JG
影响因子：
15.9
作者：
Eyerich, Stefanie;Eyerich, Kilian;Cavani, Andrea
通讯作者：
Cavani, Andrea