title: Aryl hydrocarbon receptor controls murine mast cell homeostasis.
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.
authors: Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
authors: Yufeng
authors: Y
authors: Zhou
authors: Hui-Ying
authors: HY
authors: Tung
authors: Ying-Ming
authors: YM
authors: Tsai
authors: Shih-Chang
authors: SC
authors: Hsu
authors: Hui-Wen
authors: HW
authors: Chang
authors: Hirokazu
authors: H
authors: Kawasaki
authors: Hsiao-Chun
authors: HC
authors: Tseng
authors: Beverly
authors: B
authors: Plunkett
authors: Peisong
authors: P
authors: Gao
authors: Chih-Hsing
authors: CH
authors: Hung
authors: Becky M
authors: BM
authors: Vonakis
authors: Shau-Ku
authors: SK
authors: Huang
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D017209:Apoptosis; D002118:Calcium / Q000276:immunology*; D002227:Carbazoles / Q000494:pharmacology; D015550:Cell Degranulation; D002478:Cells, Cultured; D017353:Gene Deletion; D006706:Homeostasis; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D008407:Mast Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000276:immunology; D017382:Reactive Oxygen Species / Q000276:immunology*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction
chemical_list: C111855:6-formylindolo(3,2-b)carbazole; D000941:Antigens; D002227:Carbazoles; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon; D007073:Immunoglobulin E; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D002118:Calcium