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.
Br J Dermatol. 2015;172(5):1294-302. doi: 10.1111/bjd.13621. Epub 2015 Apr 12.
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.
To identify Th2-initiating cytokines in lesional and nonlesional skin from patients with CSU and to compare the results with a control group.
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.
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.
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.
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。
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。
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。
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。
CSU 皮损中 Th2 起始细胞因子表达增加表明，先天途径可能在风团形成机制中发挥作用。由于 Th2 起始细胞因子在 CSU 中发挥着激活肥大细胞、炎症和血管渗漏的作用，这些发现也可能具有治疗意义。
