Dynamics of helper CD4 T cells during acute and stable allergic asthma

Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2...

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Published inMucosal immunology Vol. 11; no. 6; pp. 1640 - 1652
Main Authors Lu, Yanxia, Kared, Hassen, Tan, Shu Wen, Becht, Etienne, Newell, Evan W., Van Bever, Hugo P. S., Ng, Tze Pin, Larbi, Anis
Format Journal Article
LanguageEnglish
Published New York Nature Publishing Group US 01.11.2018
Elsevier Limited
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Summary:Asthma comprises heterogeneous clinical subtypes driven by diverse pathophysiological mechanisms. We characterized the modulation of the inflammatory environment with the phenotype, gene expression, and function of helper CD4 T cells among acutely exacerbated and stable asthma patients. Systemic Th2 immune deviation (IgE and Th2 cytokines) and inflammation (IL-6, CRP) were associated with increased Th17 cells during acute asthma. Th2/Th17 cell differentiation during acute asthma was regulated by the enhanced expression of transcription factors (c-MAF, IRF-4). The development of pathogenic Th2 cells during acute asthma was characterized by the secretion of inflammatory cytokines coupled with Th2 molecules and PPARγ expression. The acquisition of CD15S, CD39, CD101, and CCR4 contributed to the increased heterogeneity of Regulatory T cells during asthma. Two clusters were derived from above cytokines, CD4 T cell phenotypes, and clinical data. Cluster 1, characterized by high eosinophils, Th2 and ILC2 frequencies, and higher exacerbation rates, may represent Th2-high subtype. Cluster 2 represents a more complex subtype; it is constituted by higher neutrophils or Th17 frequencies, higher inhaled corticosteroids dose and poor asthma control. In conclusion, we characterized systematically and longitudinally Th2-high and non-Th2 asthma subtypes and the heterogeneity of CD4 T cells in stable and acute asthma. Diversity of T cells & asthma subtypes.
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ISSN:1933-0219
1935-3456
DOI:10.1038/s41385-018-0057-9