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

Eur J Immunol. 2014 Jun;44(6):1791-801. doi: 10.1002/eji.201344239. Epub 2014 Apr 15.


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.

Keywords: Chemokine; Colitis; Dextran sodium sulfate (DSS); Macrophages; Signal-transducing adaptor protein-2 (STAP-2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / immunology*
  • Allografts
  • Animals
  • Bone Marrow Transplantation
  • Cell Movement / drug effects*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Chemokine CXCL1 / genetics
  • Chemokine CXCL1 / immunology
  • Colitis / chemically induced
  • Colitis / genetics
  • Colitis / immunology*
  • Colitis / pathology
  • Dextran Sulfate / toxicity*
  • Macrophages / immunology*
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Transplantation Chimera / genetics
  • Transplantation Chimera / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology


  • Adaptor Proteins, Signal Transducing
  • Chemokine CXCL1
  • Cxcl1 protein, mouse
  • STAP2 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Dextran Sulfate