Particulate, alum or silica, was administered by intratracheal (i.t.) instillation and then we analyzed the particulate-induced lung inflammation. A histological analysis showed that, in addition to the infiltration of inflammatory cells, many lymphoid clusters, with the size of 100-300 mm in diameter, were induced in the lung. These clusters were mainly composed of B cells, and were characterized by area of B220+ and CD21+ cells, that is inducible bronchus-associated lymphoid tissue (iBALT). These clusters contained germinal center (GC) B cell area and T cell areas and generated CD138+ cells (plasmablasts), indicating that alum-induced iBALT structures function as tertiary lymphoid organ in the lung. I.t. alum instillation induced IL-1α released in the lung by alveolar macrophage (AM) cell death, and the number of iBALT formation was clearly reduced in IL-1R-deficient mice. Interestingly, IgE responses were also attenuated in IL-1R-deficient mice, coincident with decreased number of iBALT structure.
Our findings suggest that particulates induce unique immune responses in the lung through AM cell death and tertiary lymphoid organ formation, and that AM-IL-1α-iBALT axis may be a unique therapeutic target of particulate-induced allergic inflammation.