PMID:21357533

Citation	Kouzaki, H, Iijima, K, Kobayashi, T, O'Grady, SM and Kita, H (2011) The danger signal, extracellular ATP, is a sensor for an airborne allergen and triggers IL-33 release and innate Th2-type responses. J. Immunol. 186:4375-87
Abstract	The molecular mechanisms underlying the initiation of innate and adaptive proallergic Th2-type responses in the airways are not well understood. IL-33 is a new member of the IL-1 family of molecules that is implicated in Th2-type responses. Airway exposure of naive mice to a common environmental aeroallergen, the fungus Alternaria alternata, induces rapid release of IL-33 into the airway lumen, followed by innate Th2-type responses. Biologically active IL-33 is constitutively stored in the nuclei of human airway epithelial cells. Exposing these epithelial cells to A. alternata releases IL-33 extracellularly in vitro. Allergen exposure also induces acute extracellular accumulation of a danger signal, ATP; autocrine ATP sustains increases in intracellular Ca(2+) concentration and releases IL-33 through activation of P2 purinergic receptors. Pharmacological inhibitors of purinergic receptors or deficiency in the P2Y2 gene abrogate IL-33 release and Th2-type responses in the Alternaria-induced airway inflammation model in naive mice, emphasizing the essential roles for ATP and the P2Y(2) receptor. Thus, ATP and purinergic signaling in the respiratory epithelium are critical sensors for airway exposure to airborne allergens, and they may provide novel opportunities to dampen the hypersensitivity response in Th2-type airway diseases such as asthma.
Links	PubMed PMC3062674 Online version:10.4049/jimmunol.1003020
Keywords	Adenosine Triphosphate/physiology; Adenosine Triphosphate/secretion; Air Pollutants/immunology; Allergens/administration & dosage; Allergens/physiology; Alternaria/immunology; Animals; Antigens, Fungal/administration & dosage; Antigens, Fungal/immunology; Cell Line; Coculture Techniques; Extracellular Space/immunology; Extracellular Space/metabolism; Extracellular Space/microbiology; Female; Homeostasis/immunology; Humans; Immunity, Innate; Interleukin-33; Interleukins/physiology; Interleukins/secretion; Mice; Mice, 129 Strain; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Respiratory Mucosa/immunology; Respiratory Mucosa/microbiology; Respiratory Mucosa/secretion; Th2 Cells/immunology; Th2 Cells/metabolism; Th2 Cells/microbiology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:IL33		GO:0005634: nucleus	ECO:0000314:		C		Figure 3A,B shows localizations of IL33 in the nuclei of epithelial cells.	complete CACAO 11780

References

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