Pathogenic CD4+ T cells in patients with asthma

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:140

Article

Muehling, Lyndsey M.¹  Lawrence, Monica G.¹  Woodfolk, Judith A.¹ 

[1] Univ Virginia, Sch Med, Dept Med, Div Allergy, Charlottesville, VA 22908 USA

关键词: Asthma;    allergens;    IgE;    T(H)1;    T(H)2;    T(H)17;    T(H)22;    follicular helper T cell;    GATA-3;    T-bet;    thymic stromal lymphopoietin;    IL-25;    IL-33;    epithelial barrier;    T-cell epitopes;    T-cell plasticity;   

DOI  :  10.1016/j.jaci.2017.02.025

来源: Elsevier

【 摘 要 】

Asthma encompasses a variety of clinical phenotypes that involve distinct T cell-driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4(+) T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, T(H)2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of T(H)2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell hubs'' are discussed. We also describe advances in understanding the origins of atypical T(H)2 cells in asthmatic patients, the role of T(H)1 cells and other non-T(H)2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell-based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

【 授权许可】

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