Allergic airway inflammation induces upregulation of the expression of IL-23R by macrophages and not in CD3 + T cells and CD11c+F4/80− dendritic cells of the lung

Abstract

Interleukin 23 and the interleukin 23 receptor (IL-23-IL23R) are described as the major enhancing factors for Interleukin 17 (IL-17) in allergic airway inflammation. IL-17 is considered to induce neutrophilic inflammation in the lung, which is often observed in severe, steroid-resistant asthma-phenotypes. For that reason, understanding of IL-23 and IL-17 axis is very important for future therapy strategies, targeting neutrophil pathway of bronchial asthma.This study aimed to investigate the distribution and expression of IL-23R under physiological and inflammatory conditions. Therefore, a house dust mite (HDM) model of allergic airway inflammation was performed by treating mice with HDM intranasally. Immunofluorescence staining with panel of antibodies was performed in lung tissues to examine the macrophage, dendritic cell, and T cell subpopulations. The allergic airway inflammation was quantified by histopathological analysis, ELISA measurements, and airway function.HDM-treated mice exhibited a significant allergic airway inflammation including higher amounts of NE+ cells in lung parenchyma. We found only a small amount of IL-23R positives, out of total CD3+T cells, and no upregulation in HDM-treated animals. In contrast, the populations of F4/80+ macrophages and CD11c+F4/80− dendritic cells (DCs) with IL-23R expression were found to be higher. But HDM treatment leads to a significant increase of IL-23R+ macrophages, only. IL-23R was expressed by every examined macrophage subpopulation, whereas only Mϕ1 and hybrids between Mϕ1 and Mϕ2 phenotype and not Mϕ2 were found to upregulate IL-23R. Co-localization of IL-23R and IL-17 was only observed in F4/80+ macrophages, suggesting F4/80+ macrophages express IL-23R along with IL-17 in lung tissue.The study revealed that macrophages involving the IL-23 and IL-17 pathway may provide a potential interesting therapeutic target in neutrophilic bronchial asthma.

Interleukin 23 receptor: Expression and regulation in immune cells

“…Parham et al [9] found that human monocytes and dendritic cells (DC) express negligible levels of IL23R, however murine bone-marrow-derived (but not peritoneal) macrophages stimulated with LPS and IL-10 expressed Il23r in the absence of detectable Il12rb1, which could be induced by IFNγ stimulation. Inflammatory macrophages isolated from brains of mice with EAE, but not from healthy mice, expressed Il23r [3], and in a house dust mite model of airway inflammation, IL-23R positive cells in the lung were mainly macrophages and CD11 + dendritic cells [100]. These data suggest that IL-23R in myeloid cells may be expressed only in particular conditions, consistent with the lack of expression by unstimulated human myeloid cells reported in databases [101,102].…”