STAP-2 positively regulates Fc epsilon RI-mediated basophil activation and basophil-dependent allergic inflammatory reactions

Autor: Kashiwakura, Jun-ichi, Yamashita, Shinsuke, Yoshihara, Mari, Inui, Kyosuke, Saitoh, Kodai, Sekine, Yuichi, Muromoto, Ryuta, Kitai, Yuichi, Oritani, Kenji, Matsuda, Tadashi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International immunology. 31(5):349-356
ISSN: 0953-8178
Popis: Basophils 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.
Databáze: OpenAIRE