Lack of the purinergic receptor P2X7 results in resistance to contact hypersensitivity
Open Access
- 8 November 2010
- journal article
- research article
- Published by Rockefeller University Press in The Journal of Experimental Medicine
- Vol. 207 (12), 2609-2619
- https://doi.org/10.1084/jem.20092489
Abstract
Sensitization to contact allergens requires activation of the innate immune system by endogenous danger signals. However, the mechanisms through which contact allergens activate innate signaling pathways are incompletely understood. In this study, we demonstrate that mice lacking the adenosine triphosphate (ATP) receptor P2X(7) are resistant to contact hypersensitivity (CHS). P2X(7)-deficient dendritic cells fail to induce sensitization to contact allergens and do not release IL-1 beta in response to lipopolysaccharide (LPS) and ATP. These defects are restored by pretreatment with LPS and alum in an NLRP3- and ASC-dependent manner. Whereas pretreatment of wild-type mice with P2X(7) antagonists, the ATP-degrading enzyme apyrase or IL-1 receptor antagonist, prevents CHS, IL-1 beta injection restores CHS in P2X(7)-deficient mice. Thus, P2X(7) is a crucial receptor for extracellular ATP released in skin in response to contact allergens. The lack of P2X(7) triggering prevents IL-1 beta release, which is an essential step in the sensitization process. Interference with P2X(7) signaling may be a promising strategy for the prevention of allergic contact dermatitis.Keywords
This publication has 62 references indexed in Scilit:
- Contrasting Roles of the IL-1 and IL-18 Receptors in MyD88-Dependent Contact HypersensitivityJournal of Investigative Dermatology, 2010
- Immunological and Inflammatory Functions of the Interleukin-1 FamilyAnnual Review of Immunology, 2009
- Alternative Activation of Macrophages: An Immunologic Functional PerspectiveAnnual Review of Immunology, 2009
- The roles of TLRs, RLRs and NLRs in pathogen recognitionInternational Immunology, 2009
- Toll-like receptor and IL-12 signaling control susceptibility to contact hypersensitivityThe Journal of Experimental Medicine, 2008
- Environmental cues, dendritic cells and the programming of tissue-selective lymphocyte traffickingNature Immunology, 2008
- The Nlrp3 inflammasome is critical for aluminium hydroxide‐mediated IL‐1β secretion but dispensable for adjuvant activityEuropean Journal of Immunology, 2008
- Increased Level of Extracellular ATP at Tumor Sites: In Vivo Imaging with Plasma Membrane LuciferasePLOS ONE, 2008
- A pilot study of IL-1 inhibition by anakinra in acute goutArthritis Research & Therapy, 2007
- International Union of Pharmacology LVIII: Update on the P2Y G Protein-Coupled Nucleotide Receptors: From Molecular Mechanisms and Pathophysiology to TherapyPharmacological Reviews, 2006