Inducible Bronchus-Associated Lymphoid Tissue (iBALT) attenuates pulmonary Th2 responses

Abstract

Abstract Inducible bronchus-associated lymphoid tissue (iBALT) is an ectopic lymphoid tissue formed in the lung after pulmonary infection or inflammation. This local lymphoid tissue is structurally similar to conventional secondary lymphoid organs (SLOs), with separated B and T cell areas, specialized stromal cells and lymphoid dendritic cells (DCs). The presence of iBALT is typically associated with pulmonary pathology and advanced lung disease, particularly in patients with chronic obstructive pulmonary disease (COPD), rheumatoid lung disease, pulmonary fibrosis and chronic infections, suggesting that iBALT functions to exacerbate local immune responses and pathology. Here, we tested whether the presence of iBALT affected the pulmonary immune responses to allergens. We induced iBALT formation in neonatal mice by pulmonary administration of lipopolysaccharide (LPS), and when the mice were adults, sensitized and challenged them intranasally with ovalbumin (OVA). We found that mice with iBALT exhibited reduced Th2 responses, reduced eosinophil recruitment, reduced goblet cell hyperplasia and reduced mucus production. The presence of iBALT delayed the accumulation of Th2 cells and eosinophils in the lung following challenge and altered the spatial distribution of T cells in the lung. We also found that the more organized iBALT structure was, the fewer eosinophil infiltrates were observed in house dust mite (HDM)-induced allergic inflammation. Although Th2 cells are generated in mice with iBALT, they are concentrated in iBALT area and more dilute in lung parenchyma. Overall, our studies expanded the field of iBALT from observation of what happens in pulmonary diseases to determining the machinery involved in the responses.