IL-17 Induce B cells Recruitment to the Bronchial Tissue During Asthma

Background: B cells play an important role in asthma development mostly via the production of IgE. IgE levels increases in asthmatic patients both systematically and in lung tissues. However, the source behind this increase in IgE is still debatable. In this proposal, we hypothesized that IgE is increased in lung tissue of asthmatic patients due to increased infiltration of B cells to this tissue. We have recently reported elevated expression of IL-17 in severe asthma. So we suggested that IL-17 is involved in the migration of B cells to the mucosal surface of the airways.
Methods: We determined the number and pattern of infiltrated B cells into lung tissues of asthmatic compared to healthy subjects. Bronchial biopsies from asthmatic versus healthy subjects were stained for B cells marker (CD20) using Immunohistochemistry. Migration of B cells towards Th-17 cytokines were examined using Boyden Chamber migration assay. Mechanism of IL-17 induced B cell migration were tested using MAP kinase inhibitors to determine IL-17 induced MAP kinase pathways involved in this process.

Results: The number of CD20 positive cells in asthmatic biopsies was significantly higher than those in healthy subjects. Interestingly, we have also observed an increase in lymph follicle numbers in asthmatic airways compared to healthy subjects although this increase did not reach significance. Most of the lymph follicles were B cells follicles (CD20 positive cells) and were formed close to the epithelial layer.
Although B cells were shown to migrate in vitro towards both IL-17A and IL-17F, lower concentrations of IL-17F, compared to IL-17A, were sufficient to induce migration. Blocking IL-17 signaling using either anti-IL-17R antibodies or p38 MAP kinase inhibitors prevented in vitro migration of B cell towards IL-17.

Conclusion: These results indicated that IL-17 might drive the migration of B cells in the lung tissues of asthmatic patients. Activation of p38 MAP kinase seems to be required for IL-17 activity on B cells.