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Merck

Allergin-1 Immunoreceptor Suppresses House Dust Mite-Induced Allergic Airway Inflammation.

Journal of immunology (Baltimore, Md. : 1950) (2020-01-05)
Haruka Miki, Satoko Tahara-Hanaoka, Mariana Silva Almeida, Kaori Hitomi, Shohei Shibagaki, Kazumasa Kanemaru, Yu-Hsien Lin, Kanako Iwata, Shota Miyake, Shiro Shibayama, Takayuki Sumida, Kazuko Shibuya, Akira Shibuya
RESUMO

House dust mite (HDM) allergens are leading causes of allergic asthma characterized by Th2 responses. The lung-resident CD11b+ dendritic cells (DCs) play a key role in Th2 cell development in HDM-induced allergic asthma. However, the regulatory mechanism of HDM-induced CD11b+ DC activation remains incompletely understood. In this study, we demonstrate that mice deficient in an inhibitory immunoreceptor, Allergin-1, showed exacerbated HDM-induced airway eosinophilia and serum IgE elevation. By using bone marrow-chimeric mice that were sensitized with adoptively transferred HDM-stimulated wild-type or Allergin-1-deficient CD11b+ bone marrow-derived cultured DCs (BMDCs), followed by challenge with HDM, we show that Allergin-1 on the BMDCs suppressed HDM-induced allergic airway inflammation. We also show that Allergin-1 suppressed HDM-induced PGE2 production from CD11b+ BMDCs by inhibiting Syk tyrosine kinase activation through recruitment of SHP-1, subsequently leading to negative regulation of Th2 responses. These results suggest that Allergin-1 plays an important role in regulation of HDM-induced allergic airway inflammation.