IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma
IL-22, but Not IL-17, Dominant Environment in Cutaneous T-cell Lymphoma
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DOI：
10.1158/1078-0432.ccr-11-1192
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发表时间：
2011-12-15
影响因子：
11.5
通讯作者：
Sato, Shinichi
中科院分区：
文献类型：
--
作者：
Miyagaki, Tomomitsu;Sugaya, Makoto;Sato, Shinichi
目的：皮肤T细胞淋巴瘤（CTCL）和特应性皮炎（AD）患者均有瘙痒、th2偏向性T细胞和细菌感染倾向，提示这两种疾病具有共同的病理基础。最近，在AD患者的皮肤中发现了产生白细胞介素(IL)-22的T细胞。在这项研究中，我们研究了T(H)22和T(H)17相关分子在CTCL患者病变皮肤和血清中的表达水平。实验设计：收集CTCL或牛皮癣患者和健康志愿者的皮肤活检和血清。检测病变组织中IL-22、IL-17A、IL-17F、IL-23p19、IL-10、IL-4、CCL20、CCR6、IL-8和IL-20的蛋白和mRNA表达水平以及血清中这些分子的一部分。用免疫组织化学方法评估CTCL和银屑病病变皮肤中STAT3的磷酸化水平。结果：CTCL病变皮肤IL-22、IL-10、IL-4、CCL20、CCR6 mRNA和蛋白水平显著升高，IL-17A、IL-17F、IL-23p19、IL-8、IL-20水平不显著升高。CTCL皮肤表皮中检测到STAT3的磷酸化。此外，CTCL患者血清IL-22、IL-10和CCL20水平升高，且与疾病严重程度相关。结论：IL-22在CTCL肿瘤微环境的建立中起重要作用。CCL20表达的增强可能解释了表皮增生和CCR6（+）细胞（如朗格汉斯细胞）向病变皮肤的迁移。相对较低的IL-17表达可能解释了CTCL病变中中性粒细胞的缺乏，这与CTCL感染皮肤中常见的细菌感染有关。临床癌症研究；17日(24);7529 - 38。AACR (C) 2011。
Purpose: Both patients with cutaneous T-cell lymphoma (CTCL) and those with atopic dermatitis (AD) have pruritus, TH2-biased T cells, and a tendency to have bacterial infections, suggesting a common pathologic basis for these two diseases. Recently, interleukin (IL)-22-producing T cells were reported in skin of patients with AD. In this study, we investigated expression levels of T(H)22-and T(H)17-related molecules in lesional skin and sera isolated from patients with CTCL.Experimental Design: Skin biopsies and sera were collected from patients with CTCL or psoriasis and from healthy volunteers. Protein and mRNA expression levels of IL-22, IL-17A, IL-17F, IL-23p19, IL-10, IL-4, CCL20, CCR6, IL-8, and IL-20 were examined in lesional tissue and a subset of these molecules in sera. Phosphorylation of STAT3 was also assessed in lesional skin of CTCL and psoriasis by immunohistochemistry.Results: IL-22, IL-10, IL-4, CCL20, and CCR6 mRNA and protein levels, but not IL-17A, IL-17F, IL-23p19, IL-8, or IL-20, were significantly elevated in lesional skin of CTCL. Phosphorylation of STAT3 was detected in epidermis of CTCL skin. Moreover, serum IL-22, IL-10, and CCL20 levels were increased in CTCL and correlated with disease severity.Conclusions: Our results suggest that IL-22 is important in establishing the tumor microenvironment for CTCL. Enhanced expression of CCL20 may explain epidermal hyperplasia and migration of CCR6(+) cells, such as Langerhans cells, into lesional skin. Relatively low expression of IL-17 may explain the lack of neutrophils in lesions of CTCL, which correlates with bacterial infections that commonly occur in skin affected by CTCL. Clin Cancer Res; 17(24); 7529-38. (C)2011 AACR.