Pathogenic CD4 + T cells in patients with asthma

Abstract

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.

A cellular census of healthy lung and asthmatic airway wall identifies novel cell states in health and disease

“…In line with the increase in GATA3 and CD4 expression mentioned above, CD4 Th2 cells are known to be key drivers of asthma 17,36 . To assess the presence of Th2 effector cells in the airways of asthma patients (Figure 4G), we single cell sorted CD4 T cells followed by plate-based SmartSeq2 analysis for in depth transcriptional phenotyping of the T helper cell compartment (see Methods for details).…”

Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice

“…2 Recent studies have demonstrated that these pro-inflammatory cytokines undermine the structural integrity and impair the epithelial barrier of the respiratory tract. 2 Meanwhile, helminths can induce Tregs to regulate inflammatory responses by releasing anti-inflammatory cytokines, such as IL-10, TGF-β and IL-35. 30 Thus, in the present study, we detected cytokines from the splenocytes and lungs of asthmatic mice.…”

Ablation of RhoA impairs Th17 cell differentiation and alleviates house dust mite-triggered allergic airway inflammation

“…Asthma is an allergic airway inflammation affecting millions of people in the world. CD4 + Th cells, particularly Th2 cells, are traditionally believed as a key player in its pathogenesis . Recently, compelling evidence has demonstrated that Th17 cells are a major contributor to the pathogenesis of allergic airway inflammation, especially severe asthma.…”

“…CD4 + Th cells, particularly Th2 cells, are traditionally believed as a key player in its pathogenesis. [17][18][19][20] Recently, compelling evidence has demonstrated that Th17 cells are a major contributor to the pathogenesis of allergic airway inflammation, [21][22][23][24][25] especially severe asthma. The latter is often characterized by mixed responses of Th2 and Th17 cells and resistant to the steroid therapy.…”