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Journal of Diabetes Research
Volume 2015, Article ID 965056, 9 pages
Research Article

Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

1Université Paris Descartes, 75014 Paris, France
2CNRS UMR 8147, Hôpital Necker, 75015 Paris, France
3CNRS UMR 8104, Cochin Institute, 75014 Paris, France
4INSERM U1016, Cochin Institute, 75014 Paris, France
5Center of Excellence, LABEX Inflamex, 75014 Paris, France

Received 7 January 2015; Revised 13 April 2015; Accepted 15 April 2015

Academic Editor: Mark A. Yorek

Copyright © 2015 Manal Alkan et al. 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.


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.