Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell-mediated allergic response.

Abstract

Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. We show that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly.

• Authors: Di Wang, Mingzhu Zheng, Yuanjun Qiu, Chuansheng Guo, Jian Ji, Lei Lei, Xue Zhang, Jingjing Liang, Jun Lou, Wei Huang, Bowen Dong, Songquan Wu, Jianli Wang, Yuehai Ke, Xuetao Cao, Yi Ting Zhou, Linrong Lu
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 211 Issue 13 Pg. 2635-49 (Dec 15 2014) ISSN: 1540-9538 [Electronic] United States
• PMID: 25422497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wang et al.

Chemical References

• Adaptor Proteins, Signal Transducing
• Amino Acid Transport System y+
• Amino Acid Transport System y+L
• Chemokines
• FcepsilonRIalpha protein, mouse
• Fusion Regulatory Protein 1, Light Chains
• Receptors, IgE
• SLC7A8 protein, mouse
• Slc7a7 protein, mouse
• Tespa1 protein, mouse

Topics

• Adaptor Proteins, Signal Transducing (deficiency, metabolism)
• Amino Acid Transport System y+ (metabolism)
• Amino Acid Transport System y+L
• Anaphylaxis (immunology)
• Animals
• Cell Degranulation
• Cell Movement
• Chemokines (biosynthesis)
• Fusion Regulatory Protein 1, Light Chains (metabolism)
• Hypersensitivity (immunology, pathology)
• Mast Cells (immunology, pathology, physiology, ultrastructure)
• Mice, Inbred C57BL
• Mice, Knockout
• Receptors, IgE (metabolism)
• Signal Transduction (immunology)