Innate players in Th2 and non-Th2 asthma: emerging roles for the epithelial cell, mast cell, and monocyte/macrophage network.

IF 5 2区 生物学 Q2 CELL BIOLOGY American journal of physiology. Cell physiology Pub Date : 2024-12-01 Epub Date: 2024-10-14 DOI:10.1152/ajpcell.00488.2024
Johanna Kotrba, Ilka Müller, Alexander Pausder, Aaron Hoffmann, Belinda Camp, Julia D Boehme, Andreas J Müller, Jens Schreiber, Dunja Bruder, Sascha Kahlfuss, Anne Dudeck, Sabine Stegemann-Koniszewski
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Abstract

Asthma is one of the most common chronic respiratory diseases and is characterized by airway inflammation, increased mucus production, and structural changes in the airways. Recently, there is increasing evidence that the disease is much more heterogeneous than expected, with several distinct asthma endotypes. Based on the specificity of T cells as the best-known driving force in airway inflammation, bronchial asthma is categorized into T helper cell 2 (Th2) and non-Th2 asthma. The most studied effector cells in Th2 asthma include T cells and eosinophils. In contrast to Th2 asthma, much less is known about the pathophysiology of non-Th2 asthma, which is often associated with treatment resistance. Besides T cells, the interaction of myeloid cells such as monocytes/macrophages and mast cells with the airway epithelium significantly contributes to the pathogenesis of asthma. However, the underlying molecular regulation and particularly the specific relevance of this cellular network in certain asthma endotypes remain to be understood. In this review, we summarize recent findings on the regulation of and complex interplay between epithelial cells and the "nonclassical" innate effector cells mast cells and monocytes/macrophages in Th2 and non-Th2 asthma with the ultimate goal of providing the rationale for future research into targeted therapy regimens.

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Th2 和非 Th2 哮喘中的先天参与者--上皮细胞、肥大细胞和单核细胞/巨噬细胞网络的新作用。
哮喘是最常见的慢性呼吸道疾病之一,以气道炎症、粘液分泌增多和气道结构改变为特征。最近,越来越多的证据表明,这种疾病的异质性比预期的要大得多,有几种不同的哮喘内型。T 细胞是气道炎症中最著名的驱动力,根据其特异性,支气管哮喘可分为 T 辅助细胞(Th)2 型和非 Th2 型哮喘。研究最多的 Th2 哮喘效应细胞包括 T 细胞和嗜酸性粒细胞。与Th2哮喘相比,人们对非Th2哮喘的病理生理学知之甚少,而非Th2哮喘往往与抗药性有关。除 T 细胞外,单核细胞/巨噬细胞和肥大细胞等髓系细胞与气道上皮细胞的相互作用也是哮喘发病机制的重要因素。然而,这种细胞网络的潜在分子调控,特别是与某些哮喘内型的特殊相关性仍有待了解。在这篇综述中,我们总结了有关 Th2 和非 Th2 哮喘中上皮细胞与 "非典型 "先天效应细胞(肥大细胞和单核细胞/巨噬细胞)之间的调控和复杂相互作用的最新研究成果,最终目的是为今后的靶向治疗方案研究提供依据。
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来源期刊
CiteScore
9.10
自引率
1.80%
发文量
252
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Cell Physiology is dedicated to innovative approaches to the study of cell and molecular physiology. Contributions that use cellular and molecular approaches to shed light on mechanisms of physiological control at higher levels of organization also appear regularly. Manuscripts dealing with the structure and function of cell membranes, contractile systems, cellular organelles, and membrane channels, transporters, and pumps are encouraged. Studies dealing with integrated regulation of cellular function, including mechanisms of signal transduction, development, gene expression, cell-to-cell interactions, and the cell physiology of pathophysiological states, are also eagerly sought. Interdisciplinary studies that apply the approaches of biochemistry, biophysics, molecular biology, morphology, and immunology to the determination of new principles in cell physiology are especially welcome.
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