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Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice
Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene en...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452174/ https://www.ncbi.nlm.nih.gov/pubmed/26090474 http://dx.doi.org/10.1155/2015/965056 |
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author | Alkan, Manal Machavoine, François Rignault, Rachel Dam, Julie Dy, Michel Thieblemont, Nathalie |
author_facet | Alkan, Manal Machavoine, François Rignault, Rachel Dam, Julie Dy, Michel Thieblemont, Nathalie |
author_sort | Alkan, Manal |
collection | PubMed |
description | Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC(−/−) mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC(−/−) mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC(−/−) mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response. |
format | Online Article Text |
id | pubmed-4452174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-44521742015-06-18 Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice Alkan, Manal Machavoine, François Rignault, Rachel Dam, Julie Dy, Michel Thieblemont, Nathalie J Diabetes Res Research Article Recent evidence has highlighted the role of histamine in inflammation. Since this monoamine has also been strongly implicated in the pathogenesis of type-1 diabetes, we assessed its effect in the nonobese diabetic (NOD) mouse model. To this end, we used mice (inactivated) knocked out for the gene encoding histidine decarboxylase, the unique histamine-forming enzyme, backcrossed on a NOD genetic background. We found that the lack of endogenous histamine in NOD HDC(−/−) mice decreased the incidence of diabetes in relation to their wild-type counterpart. Whereas the proportion of regulatory T and myeloid-derived suppressive cells was similar in both strains, histamine deficiency was associated with increased levels of immature macrophages, as compared with wild-type NOD mice. Concerning the cytokine pattern, we found a decrease in circulating IL-12 and IFN-γ in HDC(−/−) mice, while IL-6 or leptin remained unchanged, suggesting that histamine primarily modulates the inflammatory environment. Paradoxically, exogenous histamine given to NOD HDC(−/−) mice provided also protection against T1D. Our study supports the notion that histamine is involved in the pathogenesis of diabetes, thus providing additional evidence for its role in the regulation of the immune response. Hindawi Publishing Corporation 2015 2015-05-18 /pmc/articles/PMC4452174/ /pubmed/26090474 http://dx.doi.org/10.1155/2015/965056 Text en Copyright © 2015 Manal Alkan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Alkan, Manal Machavoine, François Rignault, Rachel Dam, Julie Dy, Michel Thieblemont, Nathalie Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title_full | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title_fullStr | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title_full_unstemmed | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title_short | Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice |
title_sort | histidine decarboxylase deficiency prevents autoimmune diabetes in nod mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4452174/ https://www.ncbi.nlm.nih.gov/pubmed/26090474 http://dx.doi.org/10.1155/2015/965056 |
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