Pathogenic CD4+ T cells in patients with asthma

• Published in: Journal of allergy and clinical immunology Vol. 140; no. 6; pp. 1523 - 1540
• Main Authors: Muehling, Lyndsey M., Lawrence, Monica G., Woodfolk, Judith A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.12.2017; Elsevier Limited
• Subjects: allergens; Allergies; Allergy and Immunology; Animal models; Animals; Antigens; Asthma; Asthma - immunology; Binding sites; CD4 antigen; CD4-Positive T-Lymphocytes - immunology; Cell Differentiation; Cytokines; Dendritic cells; Disease; Disease Models, Animal; Eosinophilia; epithelial barrier; Epithelial cells; Epitopes; follicular helper T cell; GATA-3; GATA-3 protein; Gene expression; Helper cells; Human subjects; Humans; IgE; IL-25; IL-33; Immunoglobulin E; Immunotherapy; Inflammation; Kinases; Licenses; Ligands; Lymphocytes; Lymphocytes T; Lymphoid cells; Mice; Pathogenicity; Peptides; Respiratory System - immunology; Respiratory tract; Rodents; T-bet; T-cell epitopes; T-cell plasticity; TH1; Th1-Th2 Balance; TH17; TH2; TH22; Thymic stromal lymphopoietin; Thymus; Transcription factors; ILC; TCR; OX40L; IgE; IL-25; AHR; HRV; GATA-3; follicular helper T cell; ILC2; TH22; TFH; miRNA; NLRP3; T-cell plasticity; SLIT; AD; TSLP; Treg; T-bet; IL-33; BAL; Asthma; allergens; IL-4R; thymic stromal lymphopoietin; STAT; epithelial barrier; APC; MHCII; TJ; CRTH2; OVA; TH1; T-cell epitopes; Foxp3; IRF; TH17; TH2; DC; TCM; IL-4 receptor; Forkhead box p3; T H17; NLR family pyrin domain containing 3; T H2; T CM; T-cell receptor; T H1; T H22; OX40 ligand; Atopic dermatitis; Regulatory T; Dendritic cell; T FH; MHC class II; Tight junction; Interferon regulatory factor; Signal transducer and activator of transcription; Innate lymphoid cell; Human rhinovirus; Bronchoalveolar lavage; Follicular helper T; Antigen-presenting cell; Central memory T; Ovalbumin; Airway hyperreactivity; Sublingual immunotherapy; MicroRNA; Chemoattractant receptor–homologous molecule expressed on T H2 lymphocytes; Type 2 innate lymphoid cell; T(H)1; T(H)2; T(H)17; T(H)22
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2017.02.025

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, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 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 TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 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.