慢性自发性（“特发性”）荨麻疹皮损皮肤中 T 辅助 2 起始细胞因子（白细胞介素-33、白细胞介素-25 和胸腺基质淋巴细胞生成素）的升高。

Elevations in T-helper-2-initiating cytokines (interleukin-33, interleukin-25 and thymic stromal lymphopoietin) in lesional skin from chronic spontaneous ('idiopathic') urticaria.

机构信息

Leukocyte Biology Section, National Heart & Lung Institute, Imperial College London, South Kensington Campus, London SW7 2AZ, U.K.

Department of Dermatology and Allergy, Allergie-Centrum-Charité/ECARF, Charité - Universitätsmedizin, Berlin, Germany.

出版信息

Br J Dermatol. 2015;172(5):1294-302. doi: 10.1111/bjd.13621. Epub 2015 Apr 12.

DOI:10.1111/bjd.13621

PMID:25523947

Abstract

BACKGROUND

The mechanism of wealing in chronic spontaneous urticaria (CSU) is largely unknown. We previously demonstrated increased expression of T-helper 2 [interleukin (IL)-4 and IL-5] cytokines in skin biopsies from CSU. This suggested that Th2-initiating cytokines [IL-33, IL-25 and thymic stromal lymphopoietin (TSLP)], released through innate immune mechanisms, may play a role in pathogenesis.

OBJECTIVES

To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group.

METHODS

Paired biopsies (one from a 4-8 h spontaneous weal and one from uninvolved skin) were taken from eight patients with CSU and nine control subjects, and studied by immunohistochemistry and confocal microscopy.

RESULTS

There were increases in IL-4(+) and IL-5(+) cells in lesional skin vs. controls (P = 0·03 and P < 0·001, respectively) and marked elevations in the numbers of IL-33(+), IL-25(+) and TSLP(+) cells in the dermis of lesional skin vs. both nonlesional skin (P = 0·002, P = 0·01 and P = 0·04, respectively) and controls (P = 0·001, P < 0·001 and P = 0·005, respectively). There was also a correlation between the numbers of IL-33(+) and IL-25(+) cells (r = 0·808, P = 0·015). IL-33 localized to CD31(+) endothelial cells, CD90(+) fibroblasts, CD68(+) macrophages and tryptase(+) mast cells, whereas IL-25 was expressed by epithelial cells, mast cells and major basic protein-positive eosinophils. IL-33 and IL-25 were constitutively expressed in the epidermis of both controls and patients with CSU.

CONCLUSIONS

Increased expression of Th2-initiating cytokines in lesional skin in CSU suggests that innate pathways might play a role in the mechanism of wealing. As Th2-initiating cytokines play a role in mast cell activation, inflammation and vascular leakage in CSU, these findings may also have therapeutic implications.

摘要

背景

慢性自发性荨麻疹（CSU）的发病机制尚不清楚。我们之前的研究表明，CSU 皮肤活检中 T 辅助 2[白细胞介素（IL）-4 和 IL-5]细胞因子表达增加。这表明，通过先天免疫机制释放的 Th2 起始细胞因子[IL-33、IL-25 和胸腺基质淋巴细胞生成素（TSLP）]可能在发病机制中起作用。

目的

鉴定 CSU 患者皮损和非皮损皮肤中的 Th2 起始细胞因子，并与对照组进行比较。

方法

从 8 例 CSU 患者和 9 例对照者中分别采集 4-8 h 自发性风团皮损和非皮损处的配对活检标本，通过免疫组化和共聚焦显微镜进行研究。

结果

与对照组相比，皮损处的 IL-4（+）和 IL-5（+）细胞增加（P = 0.03 和 P < 0.001），且 IL-33（+）、IL-25（+）和 TSLP（+）细胞在皮损处真皮中的数量显著升高（P = 0.002、P = 0.01 和 P = 0.04），且与对照组相比也增加（P = 0.001、P < 0.001 和 P = 0.005）。IL-33（+）和 IL-25（+）细胞数量之间也存在相关性（r = 0.808，P = 0.015）。IL-33 定位于 CD31（+）内皮细胞、CD90（+）成纤维细胞、CD68（+）巨噬细胞和类胰蛋白酶（+）肥大细胞，而 IL-25 则由上皮细胞、肥大细胞和主要碱性蛋白阳性嗜酸性粒细胞表达。IL-33 和 IL-25 在对照组和 CSU 患者的表皮中均持续表达。