Pathogenic CD4 T cells in patients with asthma.

J Allergy Clin Immunol

Allergy Division, Department of Medicine, University of Virginia School of Medicine, Charlottesville, Va. Electronic address:

Published: December 2017

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, T2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of T2 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 T2 cells in asthmatic patients, the role of T1 cells and other non-T2 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651193PMC
http://dx.doi.org/10.1016/j.jaci.2017.02.025DOI Listing

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