Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis

Natsuko Fujita, Kenji Oritani, Michiko Ichii, Takafumi Yokota, Norimitsu Saitoh, Daisuke Okuzaki, Yuichi Sekine, Shigeyuki Kon, Ryuta Muromoto, Kodai Saitoh, Akihiko Yoshimura, Tadashi Matsuda, Yuzuru Kanakura

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2 Citations (Scopus)

Abstract

Signal-transducing adaptor protein-2 (STAP-2) was cloned as a c-fms/M-CSF receptor interacting protein. STAP-2 is an adaptor protein carrying pleckstrin homology and Src homology 2 like domains, as well as a YXXQ motif. STAP-2 has been indicated to have an ability to bind and modulate a variety of signaling and transcriptional molecules. Especially, our previous in vitro studies showed that STAP-2 is crucial for immune and/or inflammatory responses. Here, we have investigated the role of STAP-2 in intestinal inflammation in vivo. The disruption of STAP-2 attenuates dextran sodium sulfate induced colitis via inhibition of macrophage recruitment. To study whether hematopoietic or epithelial cell derived STAP-2 is required for this phenomenon, we generated BM chimeric mice. STAP-2-deficient macrophages impair the ability of CXCL12-induced migration. Intriguingly, STAP-2 also regulates production of proinflammatory chemokines and cytokines such as CXCL1 and TNF-α from intestinal epithelial cells. Therefore, STAP-2 has a potential to regulate plural molecular events during pathological inflammatory responses. Furthermore, our findings not only indicate that STAP-2 is important in regulating intestinal inflammation, but also provide new insights toward the development of novel therapeutic approaches.

Original languageEnglish
Pages (from-to)1791-1801
Number of pages11
JournalEuropean Journal of Immunology
Volume44
Issue number6
DOIs
Publication statusPublished - 2014 Jun

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Keywords

  • Chemokine
  • Colitis
  • Dextran sodium sulfate (DSS)
  • Macrophages
  • Signal-transducing adaptor protein-2 (STAP-2)

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Fujita, N., Oritani, K., Ichii, M., Yokota, T., Saitoh, N., Okuzaki, D., Sekine, Y., Kon, S., Muromoto, R., Saitoh, K., Yoshimura, A., Matsuda, T., & Kanakura, Y. (2014). Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis. European Journal of Immunology, 44(6), 1791-1801. https://doi.org/10.1002/eji.201344239