Human eosinophils release IL-1ß and increase expression of IL-17A in activated CD4+ T lymphocytes

• Published in: Clinical and experimental allergy Vol. 42; no. 12; pp. 1756 - 1764
• Main Authors: Esnault, S., Kelly, E. A. B., Nettenstrom, L. M., Cook, E. B., Seroogy, C. M., Jarjour, N. N.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.12.2012; Wiley Subscription Services, Inc
• Subjects: allergy; Antibodies, Monoclonal, Humanized - therapeutic use; asthma; Asthma - immunology; Asthma - therapy; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cells, Cultured; cytokines; Cytokines - genetics; Cytokines - metabolism; eosinophils; Eosinophils - immunology; Eosinophils - metabolism; Gene Expression Regulation - immunology; human; Humans; Hypersensitivity; IL-17A; IL-1ß; Interleukin-17 - genetics; Interleukin-17 - metabolism; Interleukin-1beta - genetics; Interleukin-1beta - metabolism; Lymphocyte Activation - immunology; lymphocytes; Treatment Outcome; Up-Regulation
• ISSN: 0954-7894; 1365-2222; 1365-2222
• DOI: 10.1111/j.1365-2222.2012.04060.x

Summary Background Differentiation and activation of CD4+ T cells is controlled by various cytokines produced by innate immune cells. We have shown that eosinophils (EOS) have the potential to influence Th1 and Th2 cytokine generation by CD4+ cells, but their influence on IL‐17A (IL‐17) has not been established. Objective The purpose of this study is to determine the effect of EOS on IL‐17 production by lymphocytes. Methods Pre‐activated CD4+ T cells were cultured in the presence of either autologous EOS or EOS culture supernatants. Expression of IL‐17 was determined by real‐time quantitative PCR (qPCR) after 5 h and protein level was measured after 48 h. To determine the effect of allergen‐induced airway EOS on IL‐17, subjects with mild allergic asthma underwent bronchoscopic segmental bronchoprovocation with allergen (SBP‐Ag) after a treatment with an anti‐IL‐5 neutralizing antibody (mepolizumab) to reduce airway eosinophilia. IL‐17 mRNA was measured in bronchoalveolar lavage (BAL) cells by qPCR. Results In vitro, EOS significantly increased IL‐17 production by CD4+ T cells. Addition of exogenous IL‐1ß increased expression of IL‐17 mRNA by CD4+ T cells. EOS expressed and released IL‐1ß. Furthermore, levels of IL‐1ß in EOS supernatants highly correlated with their ability to increase IL‐17 expression by CD4+ T cells, and neutralizing antibody to IL‐1ß reduced expression of IL‐17 mRNA. In vivo, reduction of EOS in the airway using mepolizumab was associated with diminished IL‐17 expression after SBP‐Ag. Conclusions and clinical relevance Our data demonstrate that EOS can promote IL‐17 production through the release of IL‐1ß. Enhanced IL‐17 cytokine production is another mechanism by which EOS may participate in pathogenesis of allergic airway inflammation in asthma.