Tespa1 Negatively Regulates FcεRI-mediated Signaling and the Mast Cell-mediated Allergic Response

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2014 Nov 26

PMID 25422497

Citations 9

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

Affiliations

Soon will be listed here.

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.

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