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Rcan1 negatively regulates FcRI-mediated signaling and mast cell function

¹ Department of Microbiology and Immunology and Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia B3K 6R8, Canada
² Department of Immunology, Capital Medical University, Beijing 100069, China
³ Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH 45229

CORRESPONDENCE Tong-Jun Lin: tong-jun.lin{at}dal.ca

Aggregation of the high affinity IgE receptor (FcRI) activates a cascade of signaling events leading to mast cell activation. Subsequently, inhibitory signals are engaged for turning off activating signals. We identified that regulator of calcineurin (Rcan) 1 serves as a negative regulator for turning off FcRI-mediated mast cell activation. FcRI-induced Rcan1 expression was identified by suppression subtractive hybridization and verified by real-time quantitative polymerase chain reaction and Western blotting. Deficiency of Rcan1 led to increased calcineurin activity, increased nuclear factor of activated T cells and nuclear factor B activation, increased cytokine production, and enhanced immunoglobulin E–mediated late-phase cutaneous reactions. Forced expression of Rcan1 in wild-type or Rcan1-deficient mast cells reduced FcRI-mediated cytokine production. Rcan1 deficiency also led to increased FcRI-mediated mast cell degranulation and enhanced passive cutaneous anaphylaxis. Analysis of the Rcan1 promoter identified a functional Egr1 binding site. Biochemical and genetic evidence suggested that Egr1 controls Rcan1 expression. Our results identified Rcan1 as a novel inhibitory signal in FcRI-induced mast cell activation and established a new link of Egr1 and Rcan1 in FcRI signaling.

© 2009 Yang et al.
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This article has been cited by other articles:

• Yang, Y. J., Chen, W., Edgar, A., Li, B., Molkentin, J. D., Berman, J. N., Lin, T.-J. (2009). Rcan1 negatively regulates FceRI-mediated signaling and mast cell function. JCB 184: i2-i2 [Full Text]  

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