Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.
Progressive activation of T(H)2/T(H)22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis.
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DOI：
10.1016/j.jaci.2012.07.012
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发表时间：
2012-12
影响因子：
14.2
通讯作者：
Guttman-Yassky, Emma
中科院分区：
文献类型：
--
作者：
Gittler, Julia K.;Shemer, Avner;Suarez-Farinas, Mayte;Fuentes-Duculan, Judilyn;Gulewicz, Kara J.;Wang, Claire Q. F.;Mitsui, Hiroshi;Cardinale, Irma;Strong, Cristina de Guzman;Krueger, James G.;Guttman-Yassky, Emma
特应性皮炎（AD）是一种常见病，发病率逐年上升。该病的主要发病机制仍不清楚，导致缺乏特异性治疗。AD目前被认为是一种双相疾病，其中Th 2占主导地位的急性疾病，以及向Th 1转变的慢性疾病。阐明参与新病变的发生和慢性疾病的维持的分子因素对于靶向治疗的发展至关重要。我们试图描述AD发病和维持的机制。我们通过基因组、分子和细胞分析研究了10名AD患者的非病变、急性和慢性病变的个人内转录组。我们的研究将急性病变的发生与终末分化蛋白亚组的显著增加相关联，特别是精氨酸调节的S100 A7、S100 A8和S100 A9。急性疾病还与主要Th 22-和Th 2-细胞因子的基因表达水平的显著增加以及IL-17的较小增加相关。在急性疾病中检测到较少的Th 1相关基因诱导，尽管有些在慢性疾病中显著上调。在急性和慢性病变之间观察到主要Th 22和Th 2细胞因子的进一步显著增强。我们的数据确定了S100 A7、S100 A8和S100 A9基因表达随着AD的启动而增加，并且伴随着Th 2和Th 22细胞因子的激活。我们的研究结果支持一个模型的Th 2和Th 22免疫轴从急性到慢性阶段进行性激活，扩大流行的发病机制的观点，具有重要的治疗意义。
Atopic dermatitis (AD) is a common disease, with an increasing prevalence. The primary pathogenesis of the disease is still elusive, resulting in the lack of specific treatments. AD is currently considered a biphasic disease, with Th2 predominating acute disease, and a switch to Th1 characterizing chronic disease. Elucidation of the molecular factors that participate in the onset of new lesions and maintenance of chronic disease is critical for the development of targeted therapeutics. We sought to characterize the mechanisms underlying onset and maintenance of AD. We investigated intrapersonal sets of transcriptomes from non-lesional, acute and chronic lesions of ten AD patients through genomic, molecular and cellular profiling. Our study associated the onset of acute lesions with a striking increase in a subset of terminal differentiation proteins, specifically the cytokine-modulated S100A7, S100A8, and S100A9. Acute disease was also associated with significant increases in gene expression levels of major Th22- and Th2- cytokines, and smaller increases in IL-17. A lesser induction of Th1-associated genes was detected in acute disease, although some were significantly up-regulated in chronic disease. Further significant intensification of major Th22 and Th2 cytokines was observed between acute and chronic lesions. Our data identified increased S100A7, S100A8 and S100A9 gene expression with AD initiation, and concomitant activation of Th2 and Th22 cytokines. Our findings support a model of progressive activation of Th2 and Th22 immune axes from acute to chronic phases, expanding the prevailing view of pathogenesis, with important therapeutic implications.
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影响因子：
6.5
作者：
GREWE, M;WALTHER, S;KRUTMANN, J
通讯作者：
KRUTMANN, J
影响因子：
2.3
作者：
Bonder, CS;Davies, KVL;Hart, PH
通讯作者：
Hart, PH
影响因子：
14.2
作者：
Hamid, Q;Naseer, T;Leung, DYM
通讯作者：
Leung, DYM
影响因子：
14.2
作者：
Guttman-Yassky, Emma;Nograles, Kristine E.;Krueger, James G.
通讯作者：
Krueger, James G.
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