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GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice
BACKGROUND: 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 inflammat...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324651/ https://www.ncbi.nlm.nih.gov/pubmed/27527650 http://dx.doi.org/10.1111/all.13005 |
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author | Rubić‐Schneider, T. Carballido‐Perrig, N. Regairaz, C. Raad, L. Jost, S. Rauld, C. Christen, B. Wieczorek, G. Kreutzer, R. Dawson, J. Lametschwandner, G. Littlewood‐Evans, A. Carballido, J. M. |
author_facet | Rubić‐Schneider, T. Carballido‐Perrig, N. Regairaz, C. Raad, L. Jost, S. Rauld, C. Christen, B. Wieczorek, G. Kreutzer, R. Dawson, J. Lametschwandner, G. Littlewood‐Evans, A. Carballido, J. M. |
author_sort | Rubić‐Schneider, T. |
collection | PubMed |
description | BACKGROUND: 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. METHODS: 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. RESULTS: 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 as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: 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. |
format | Online Article Text |
id | pubmed-5324651 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-53246512017-03-08 GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice Rubić‐Schneider, T. Carballido‐Perrig, N. Regairaz, C. Raad, L. Jost, S. Rauld, C. Christen, B. Wieczorek, G. Kreutzer, R. Dawson, J. Lametschwandner, G. Littlewood‐Evans, A. Carballido, J. M. Allergy ORIGINAL ARTICLES BACKGROUND: 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. METHODS: 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. RESULTS: 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 as augmented mast cell responses could be recapitulated in wt mast cells differentiated in the absence of succinate. CONCLUSIONS: 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. John Wiley and Sons Inc. 2016-09-12 2017-03 /pmc/articles/PMC5324651/ /pubmed/27527650 http://dx.doi.org/10.1111/all.13005 Text en © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | ORIGINAL ARTICLES Rubić‐Schneider, T. Carballido‐Perrig, N. Regairaz, C. Raad, L. Jost, S. Rauld, C. Christen, B. Wieczorek, G. Kreutzer, R. Dawson, J. Lametschwandner, G. Littlewood‐Evans, A. Carballido, J. M. GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title |
GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title_full |
GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title_fullStr |
GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title_full_unstemmed |
GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title_short |
GPR91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
title_sort | gpr91 deficiency exacerbates allergic contact dermatitis while reducing arthritic disease in mice |
topic | ORIGINAL ARTICLES |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324651/ https://www.ncbi.nlm.nih.gov/pubmed/27527650 http://dx.doi.org/10.1111/all.13005 |
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