核糖核酸酶 7 通过下调激活的人 T 细胞中的 TH2 细胞因子产生。

RNase 7 downregulates TH2 cytokine production by activated human T cells.

机构信息

Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Hannover, Germany.

Department of Dermatology, University Hospital Schleswig-Holstein, Kiel, Germany.

出版信息

Allergy. 2017 Nov;72(11):1694-1703. doi: 10.1111/all.13173. Epub 2017 Jun 21.

DOI:10.1111/all.13173

PMID:28378334

Abstract

BACKGROUND

The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells.

METHODS

Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay.

RESULTS

Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7.

CONCLUSION

Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.

摘要

背景

抗菌肽（AMP）RNase 7 在健康人的皮肤表皮中持续表达，并且在特应性皮炎和银屑病等慢性炎症性皮肤病中发现其上调。特应性皮炎（AD）和银屑病（PSO）患者皮损皮肤中的活化 T 细胞可能直接暴露于 RNase 7。除了其抗菌活性外，几种 AMP 的免疫调节功能已被发表。在这项研究中，我们研究了抗菌肽 RNase 7 对活化 T 细胞的免疫调节作用。

方法

用 RNase 7 刺激分离的人 CD3+T 细胞，并通过 mRNA 微阵列分析筛选可能的作用。使用皮肤来源的天然 RNase 7 和重组无核糖核酸酶活性的 RNase 7 突变体，在分离的 CD4+T 细胞和极化的 TH2 细胞中确认了 mRNA 微阵列的结果。通过电泳迁移率变动分析分析 GATA3 的激活。

结果

用 RNase 7 处理活化的人 CD4+T 细胞和 TH2 细胞选择性地降低了 TH2 细胞因子（IL-13、IL-4 和 IL-5）的表达。用无核糖核酸酶活性的重组 RNase 7 突变体的实验表明，RNase 7 的核糖核酸酶活性对于观察到的调节作用是可有可无的。我们进一步证明，与健康对照相比，AD 患者的 CD4+T 细胞对 RNase 7 的反应明显较少下调 IL-13。最后，我们表明，用 RNase 7 培养 T 细胞可减弱 GATA3 的激活。