Innate and adaptive T cells in asthmatic patients: Relationship to severity and disease mechanisms

作者：Timothy Hinks, Xiaoying Zhou, Karl J. Staples, Borislav D. Dimitrov, Alexander Manta, Tanya C. Petrossian, Pek Yee Lum, Caroline G. Smith, Jonathan Ward, Peter Hugo Howarth, Andrew F. Walls, Stephan Donat Gadola, Ratko Djukanović · 发表于：Journal of Allergy and Clinical Immunology · 年份：2015 · DOI：10.1016/j.jaci.2015.01.014 · 被引用次数：236 · 研究领域：Asthma and respiratory diseases、IL-33, ST2, and ILC Pathways、Immune Cell Function and Interaction

BACKGROUND: Asthma is a chronic inflammatory disease involving diverse cells and mediators whose interconnectivity and relationships to asthma severity are unclear. OBJECTIVE: We performed a comprehensive assessment of TH17 cells, regulatory T cells, mucosal-associated invariant T (MAIT) cells, other T-cell subsets, and granulocyte mediators in asthmatic patients. METHODS: Sixty patients with mild-to-severe asthma and 24 control subjects underwent detailed clinical assessment and provided induced sputum, endobronchial biopsy, bronchoalveolar lavage, and blood samples. Adaptive and invariant T-cell subsets, cytokines, mast cells, and basophil mediators were analyzed. RESULTS: Significant heterogeneity of T-cell phenotypes was observed, with levels of IL-13-secreting T cells and type 2 cytokines increased at some, but not all, asthma severities. TH17 cells and γδ-17 cells, proposed drivers of neutrophilic inflammation, were not strongly associated with asthma, even in severe neutrophilic forms. MAIT cell frequencies were strikingly reduced in both blood and lung tissue in relation to corticosteroid therapy and vitamin D levels, especially in patients with severe asthma in whom bronchoalveolar lavage regulatory T-cell numbers were also reduced. Bayesian network analysis identified complex relationships between pathobiologic and clinical parameters. Topological data analysis identified 6 novel clusters that are associated with diverse underlying disease mechanisms, with increased...