GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice

Autor: Grazyna Wieczorek, G. Lametschwandner, José M. Carballido, Amanda Littlewood-Evans, S. Jost, Tina Rubic-Schneider, Camille Regairaz, Brigitte Christen, Layla Raad, Janet Dawson, Nicole Carballido-Perrig, Celine Rauld, R. Kreutzer
Rok vydání: 2016
Předmět:
0301 basic medicine
Allergy
immunometabolism
Arthritis
Immunoglobulin E
medicine.disease_cause
Receptors
G-Protein-Coupled
Autoimmunity
Mice
0302 clinical medicine
Immunology and Allergy
Mast Cells
Mice
Knockout
biology
alarmins
autoimmunity
Mast cell
medicine.anatomical_structure
Experimental Allergy and Immunology
030220 oncology & carcinogenesis
Dermatitis
Allergic Contact
Disease Progression
Cytokines
Original Article
Inflammation Mediators
Immunology
03 medical and health sciences
Immune system
In vivo
medicine
Animals
Humans
Genetic Predisposition to Disease
Allergic contact dermatitis
Genetic Association Studies
business.industry
Macrophages
Macrophage Activation
allergy
succinate
medicine.disease
Disease Models
Animal
030104 developmental biology
biology.protein
ORIGINAL ARTICLES
business
Biomarkers
Gene Deletion
Zdroj: Allergy
ISSN: 0105-4538
Popis: Succinate, in addition to its role as an intermediary of the citric acid cycle, acts as an alarmin, initiating and propagating danger signals resulting from tissue injury or inflammatory stimuli. The contribution of this immune sensing pathway to the development of allergic and inflammatory responses is unknown. Ear thickness of wild type (wt) and Sucnr1 deficient (Sucnr1 (-/-) ) mice, sensitized and challenged with oxazolone, was used as a criterion to assess the relevance of SUCNR1/GPR91 expression mediating allergic contact dermatitis (ACD). Results obtained in this system were contrasted with data generated using passive cutaneous anaphylaxis, ovalbumin-induced asthma and arthritis models. We found augmented ACD reactions in Sucnr1(-/-) mice. This observation correlated with increased mast cell activation in vitro and in vivo. However, exacerbated mast cell activation in Sucnr1(-/-) mice did not contribute to the enhancement of asthma or arthritis and seemed to be due to alterations during mast cell development since augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. A deficiency in succinate sensing during mast cell development confers these cells with a hyperactive phenotype. Such a phenomenon does not translate into exacerbation of asthma or mast cell dependent arthritis. On the contrary, the fact that Sucnr1(-/-) mice developed reduced arthritic disease, using two different in vivo models, indicates that GPR91 antagonists may have therapeutic potential for the treatment of allergic and autoimmune diseases. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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