TY - JOUR
T1 - Aryl hydrocarbon receptor controls murine mast cell homeostasis
AU - Zhou, Yufeng
AU - Tung, Hui Ying
AU - Tsai, Ying Ming
AU - Hsu, Shih Chang
AU - Chang, Hui Wen
AU - Kawasaki, Hirokazu
AU - Tseng, Hsiao Chun
AU - Plunkett, Beverly
AU - Gao, Peisong
AU - Hung, Chih Hsing
AU - Vonakis, Becky M.
AU - Huang, Shau Ku
N1 - Funding Information:
This work was supported in part by grants from the National Institutes of Health (AI052468 and AI073610), the National Health Research Institutes of Taiwan (EOPP10-014 and EOSP07-014), and the National Science Council of Taiwan (NSC 100-3114-Y-043-002/ 00D1-EODOH01).
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2012-08-453597
DO - 10.1182/blood-2012-08-453597
M3 - Article
C2 - 23462117
AN - SCOPUS:84879181079
SN - 0006-4971
VL - 121
SP - 3195
EP - 3204
JO - Blood
JF - Blood
IS - 16
ER -