Antigen-specific airway IL-33 production depends on FcR-mediated incorporation of the antigen by alveolar macrophages in sensitized mice

作者：Nabe Takeshi; Matsuda Masaya; Ishida Tomoki; Tsujimoto Nau; Kido Hitomi; Kanaya Haruna; Takahashi Hiromu; Takemoto Naoki; Nomura Miku; Ishihara Keiichi; Akiba Satoshi; Mizutani Nobuaki

来源：Immunology, 2018, 155(1): 99-111.

DOI：10.1111/imm.12931

• airway inflammation
• B-cells
• IgG
• interleukin-33
• macrophages

Although interleukin (IL)-33 is a candidate for the aggravation of asthma, the mechanisms underlying antigen-specific IL-33 production in the lung are unclear. Therefore, we analysed the mechanisms in mice. Intra-tracheal administration of ovalbumin (OVA) evoked increases in IL-33 and IL-33 mRNA in the lungs of both non-sensitized and OVA-sensitized mice, and the increases in the sensitized mice were significantly higher than in the non-sensitized mice. However, intra-tracheal administration of bovine serum albumin did not increase the IL-33 level in the OVA-sensitized mice. Depletion of neither mast cells/basophils nor CD4(+) cells abolished the OVA-induced IL-33 production in sensitized mice, suggesting that the antigen recognition leading to the IL-33 production was not related with either antigen-specific IgE-bearing mast cells/basophils or memory CD4(+) Th2 cells. When a fluorogenic substrate-labelled OVA (DQ-OVA) was intra-tracheally administered, the lung cells of sensitized mice incorporated more DQ-OVA than those of non-sensitized mice. The lung cells incorporating DQ-OVA included B-cells and alveolar macrophages. The allergic IL-33 production was significantly reduced by treatment with anti-FcRII/III mAb. Depletion of alveolar macrophages by clodronate liposomes significantly suppressed the allergic IL-33 production, whereas depletion of B-cells by anti-CD20 mAb did not. These results suggest that the administered OVA in the lung bound antigen-specific IgG Ab, and then alveolar macrophages incorporated the immune complex through FcRII/III on the cell surface, resulting in IL-33 production in sensitized mice. The mechanisms underlying the antigen-specific IL-33 production may aid in development of new pharmacotherapies.

• 出版日期2018-9