Human Eosinophils Release IL-1ß and Increase Expression of IL-17A in Activated CD4+ T Lymphocytes

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.