Aryl hydrocarbon receptor controls murine mast cell homeostasis

Yufeng Zhou, Hui Ying Tung, Ying Ming Tsai, Shih Chang Hsu, Hui Wen Chang, Hirokazu Kawasaki, Hsiao Chun Tseng, Beverly Plunkett, Peisong Gao, Chih Hsing Hung, Becky M. Vonakis, Shau Ku Huang

Research output: Contribution to journalArticle

Abstract

We propose that the aryl hydrocarbon receptor (AhR), a unique chemical sensor, is critical in controlling mast cell differentiation, growth, and function in vitro and in vivo. In antigen-stimulated mast cells, exposure to AhR ligands resulted in a calcium- and reactive oxygen species (ROS)-dependent increase of reversible oxidation in and reduced activity of SHP-2 phosphatase, leading to enhanced mast cell signaling, degranulation, and mediator and cytokine release, as well as the in vivo anaphylactic response. Surprisingly, significant mast cell deficiency was noted in AhR-null mice due to defective calcium signaling and mitochondrial function, concomitant with reduced expression of c-kit and cytosolic STAT proteins, as well as enhanced intracellular ROS and apoptosis. Consequently, AhR-null mast cells responded poorly to stimulation, demonstrating a critical role of AhR signaling in maintaining mast cell homeostasis.

Original languageEnglish (US)
Pages (from-to)3195-3204
Number of pages10
JournalBlood
Volume121
Issue number16
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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  • Cite this

    Zhou, Y., Tung, H. Y., Tsai, Y. M., Hsu, S. C., Chang, H. W., Kawasaki, H., Tseng, H. C., Plunkett, B., Gao, P., Hung, C. H., Vonakis, B. M., & Huang, S. K. (2013). Aryl hydrocarbon receptor controls murine mast cell homeostasis. Blood, 121(16), 3195-3204. https://doi.org/10.1182/blood-2012-08-453597