Saturday, 17 October 2015
Hall D1 Foyer (Floor 3) (Coex Convention Center)
Etsushi Kuroda, PhD
,
Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
Koji Ozasa, MD
,
Department of Pediatrics, Yokohama City University Graduate School of Medicine, Yokohama, Japan
Ken Ishii, MD, PhD
,
Laboratory of Vaccine Science, WPI Immunology Frontier Research Center, Osaka University, Suita, Japan
Recently, the number of patients suffering from allergic diseases such as asthma or rhinitis has increased especially in developed countries. The reason is unclear, but many study have demonstrated that particle pollutants such as diesel exhaust and sand dust may exacerbate allergic responses. Furthermore, several nanometer- to micrometer-sized tiny particulates, such as particulate matter 2.5 (PM2.5) that is less than 2.5 micrometers in diameter, could enter into the respiratory tract and settle deep in lungs, causing pulmonary chronic inflammation such as asthma. Most particulates including particle pollutants are considered to function as immune adjuvants to enhance allergen-specific type 2 responses. However, the basis for the adjuvanticity of these particulates and the mechanisms by which they elicit type 2 responses remain poorly understood. Here, we show that particulate induce inducible bronchus-associated lymphoid tissue (iBALT) in the lung as a consequence of cell death of alveolar macrophages and IL-1α release.
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.
