Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand; INSERM UMR1149, CNRS ERL8252, Centre de recherche sur l'inflammation, Inflamex, Université de Paris, Paris, France.
Malaghan Institute of Medical Research, Victoria University, Wellington, New Zealand.
J Allergy Clin Immunol. 2021 Sep;148(3):799-812.e10. doi: 10.1016/j.jaci.2021.02.018. Epub 2021 Mar 2.
The type 2 cytokines IL-4 and IL-13 promote not only atopic dermatitis (AD) but also the resolution of inflammation. How type 2 cytokines participate in the resolution of AD is poorly known.
Our aim was to determine the mechanisms and cell types governing skin inflammation, barrier dysfunction, and resolution of inflammation in a model of AD.
Mice that exhibit expression of IL-4, IL-13, and MCPT8 or that could be depleted of basophils or eosinophils, be deficient in IL-4 or MHC class II molecules, or have basophils lacking macrophage colony-stimulating factor (M-CSF) were treated with calcipotriol (MC903) as an acute model of AD. Kinetics of the disease; keratinocyte differentiation; and leukocyte accumulation, phenotype, function, and cytokine production were measured by transepidermal water loss, histopathology, molecular biology, or unbiased analysis of spectral flow cytometry.
In this model of AD, basophils were activated systemically and were the initial and main source of IL-4 in the skin. Basophils and IL-4 promoted epidermal hyperplasia and skin barrier dysfunction by acting on keratinocyte differentiation during inflammation. Basophils, IL-4, and basophil-derived M-CSF inhibited the accumulation of proinflammatory cells in the skin while promoting the expansion and function of proresolution M2-like macrophages and the expression of probarrier genes. Basophils kept their proresolution properties during AD resolution.
Basophils can display both beneficial and detrimental type 2 functions simultaneously during atopic inflammation.
2 型细胞因子 IL-4 和 IL-13 不仅促进特应性皮炎（AD），还促进炎症的消退。2 型细胞因子如何参与 AD 的消退知之甚少。
我们的目的是确定在 AD 模型中控制皮肤炎症、屏障功能障碍和炎症消退的机制和细胞类型。
表达 IL-4、IL-13 和 MCPT8 的小鼠，或可以耗尽嗜碱性粒细胞或嗜酸性粒细胞、缺乏 IL-4 或 MHC Ⅱ类分子、或缺乏巨噬细胞集落刺激因子（M-CSF）的嗜碱性粒细胞的小鼠，用钙泊三醇（MC903）治疗作为 AD 的急性模型。通过经表皮水分丢失、组织病理学、分子生物学或无偏析光谱流式细胞术分析，测量疾病的动力学、角质形成细胞分化以及白细胞的积累、表型、功能和细胞因子的产生。
在这个 AD 模型中，嗜碱性粒细胞在全身被激活，是皮肤中 IL-4 的初始和主要来源。嗜碱性粒细胞和 IL-4 通过在炎症过程中作用于角质形成细胞分化，促进表皮增生和皮肤屏障功能障碍。嗜碱性粒细胞、IL-4 和嗜碱性粒细胞衍生的 M-CSF 抑制促炎细胞在皮肤中的积累，同时促进抗炎 M2 样巨噬细胞的扩张和功能以及屏障基因的表达。嗜碱性粒细胞在 AD 缓解期间保持其抗炎特性。
在特应性炎症期间，嗜碱性粒细胞可以同时显示出有益和有害的 2 型功能。
