Signal-transducing adaptor protein-2 controls the IgE-Mediated, mast cell-mediated anaphylactic responses

Yuichi Sekine, Keigo Nishida, Satoru Yamasaki, Ryuta Muromoto, Shigeyuki Kon, Jun Ichi Kashiwakura, Kodai Saitoh, Sumihito Togi, Akihiko Yoshimura, Kenji Oritani, Tadashi Matsuda

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Signal-transducing adaptor protein-2 (STAP-2) is a recently identified adaptor protein that regulates immune and inflammatory responses through interactions with a variety of signaling and transcriptional molecules. In the current study, we clarified the physiological role of STAP-2 in mast cell function, a key mediator of IgE-associated allergic responses. STAP-2 is constitutively expressed in mast cells. STAP-2 deficiency in mast cells greatly enhances FcRI-mediated signals, resulting in the increased tyrosine phosphorylation of the phospholipase C-g isoform, calcium mobilization, and degranulation. Of importance, STAP-2-deficient mice challenged with DNP-BSA after passive sensitization with anti-DNP IgE show more severe rectal temperature decrease than do wild-type mice. STAP-2-deficient mice also show increased vascular permeability and more severe cutaneous anaphylaxis after DNP-BSA injection. These regulatory functions performed by STAP-2 indicate that there is an interaction between STAP-2 and FcRI. In addition, our previous data indicate that STAP-2 binds to the phospholipase C-g isoform and IkB kinase-b. Therefore, our data described in this article strongly suggest that manipulation of STAP-2 expression in mast cells may control the pathogenesis of allergic diseases and have the potential for treating patients with allergy.

Original languageEnglish
Pages (from-to)3488-3495
Number of pages8
JournalJournal of Immunology
Volume192
Issue number8
DOIs
Publication statusPublished - 2014 Apr 15

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sekine, Y., Nishida, K., Yamasaki, S., Muromoto, R., Kon, S., Kashiwakura, J. I., Saitoh, K., Togi, S., Yoshimura, A., Oritani, K., & Matsuda, T. (2014). Signal-transducing adaptor protein-2 controls the IgE-Mediated, mast cell-mediated anaphylactic responses. Journal of Immunology, 192(8), 3488-3495. https://doi.org/10.4049/jimmunol.1300886