First Author | Zhou Y | Year | 2013 |
Journal | Blood | Volume | 121 |
Issue | 16 | Pages | 3195-204 |
PubMed ID | 23462117 | Mgi Jnum | J:197552 |
Mgi Id | MGI:5493363 | Doi | 10.1182/blood-2012-08-453597 |
Citation | Zhou Y, et al. (2013) Aryl hydrocarbon receptor controls murine mast cell homeostasis. Blood 121(16):3195-204 |
abstractText | 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. |