Circulating T cells, natural killer (NK) cells and group 2 innate lymphoid cells (ILC2) of severe asthmapatients from the University of California Asthma Network (UCANTM) clinic, express increased levels of both IL-13 and IL-17

Rationale: Neutrophilic inflammation and IL-17 have been implicated in the pathogenesis of severe asthma but the underlying mechanisms remain unclear. We aimed to establish the relationship between inflammatory markers of severe asthma and peripheral blood dendritic cell and lymphocyte populations and their IL-13 and IL-17 expression.

Methods: Twenty-seven patients with severe asthma all requiring asthma medications and seven non-asthmatic healthy controls were recruited from the UCAN^TMclinic at the University of California, Davis. Complete blood count, exhaled NO and serum IgE/IgM were investigated. Peripheral blood mononuclear cells were isolated by Ficoll-Paque PLUS and T-cell subsets, dendritic cell subsets, natural killer cells and ILC2 were analyzed by multi-color flow cytometry and compared between the patients and healthy controls.

Results: Severe asthma patients had elevated blood neutrophil counts, exhaled NO, serum IgE and IgM. In comparison with healthy controls, the number of circulating CD1c dendritic cells, CD4 T cells, NK cells and ILC2 were significantly increased (p<0.05). Further, the number of CD141 DC (implicated in activation of Th2 cells) significantly correlated with peripheral blood eosinophils (r=0.70) and CD4 T cells. Intracellular IL-13 and IL-17a expression was significantly elevated in CD4 and CD8 T cells, NK cells and ILC2.

Conclusions: We showed for the first time the presence of ILC2 producing both IL-13 and IL-17, in the peripheral blood of severe asthma patients. Our data also support that increased IL-17 expression may contribute to the elevated neutrophil count we observed in severe asthma patients.