2024-03-28T21:23:50Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/782482022-11-17T02:08:08Zhdl_2115_20044hdl_2115_124STAP-2 positively regulates Fc epsilon RI-mediated basophil activation and basophil-dependent allergic inflammatory reactionsKashiwakura, Jun-ichiYamashita, ShinsukeYoshihara, MariInui, KyosukeSaitoh, KodaiSekine, YuichiMuromoto, RyutaKitai, YuichiOritani, KenjiMatsuda, TadashibasophilsIgEIgE-CAIIL-4STAP-2460Basophils are an important cell type in the regulation of T(h)2 immune responses. Recently, we revealed that signal-transducing adaptor protein-2 (STAP-2) negatively regulates mast cell activation via Fc epsilon RI. However, the role of STAP-2 in basophil maturation and activation remained unclear. In this study, we demonstrated the normal development of basophils in STAP-2-deficient (STAP-2(-/-)) mice. We also demonstrated in vitro normal basophil differentiation and FceRI expression in STAP2(-/-) mice, suggesting that STAP-2 is dispensable for basophil maturation. Using bone marrow-derived cultured basophils (BMBs), we showed that degranulation and cytokine production of STAP-2(-/-) BMBs were lower than those of wild-type (WT) BMBs upon stimulation with IgE/Ag. In accordance with the reduction of degranulation and cytokine production, phosphorylation of several signal molecules such as Lyn, PLC-gamma 2 and Erk was reduced in STAP-2(-/-) BMBs after stimulation via Fc epsilon RI. Finally, it was observed that IgE-dependent chronic allergic inflammation of STAP-2(-/-) mice was significantly inhibited compared with WT mice. Taken together, we conclude that STAP-2 is an adaptor molecule that positively regulates FceRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions.Oxford University PressJournal Articleapplication/pdfhttp://hdl.handle.net/2115/78248https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/78248/1/WoS_91370_Kashiwakura.pdf0953-8178International immunology3153493562019-05enginfo:doi/10.1093/intimm/dxz013This is a pre-copyedited, author-produced version of an article accepted for publication in International Immunology following peer review. The version of record Jun-ichi Kashiwakura et al. STAP-2 positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions. International Immunology, Volume 31, Issue 5, May 2019, Pages 349–356. is available online at: https://doi.org/10.1093/intimm/dxz013author