Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice

Autor: François Machavoine, Michel Dy, Rachel Rignault, Nathalie Thieblemont, Julie Dam, Manal Alkan
Přispěvatelé: Institut Cochin (UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Cytokines, hématopoïèse et réponse immune (CHRI), This work was supported by grants from the Fondation DaySolvay and the CNRS, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bos, Mireille
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Leptin
medicine.medical_specialty
Article Subject
Endocrinology
Diabetes and Metabolism
medicine.medical_treatment
Inflammation
Nod
Biology
Histidine Decarboxylase
lcsh:Diseases of the endocrine glands. Clinical endocrinology
T-Lymphocytes
Regulatory
Pathogenesis
03 medical and health sciences
chemistry.chemical_compound
Interferon-gamma
Mice
0302 clinical medicine
Endocrinology
Immune system
Mice
Inbred NOD
Internal medicine
medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Animals
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
NOD mice
Mice
Knockout
0303 health sciences
lcsh:RC648-665
Interleukin-6
Histidine decarboxylase
Interleukin-12
3. Good health
Cytokine
Diabetes Mellitus
Type 1
chemistry
Immunology
Cytokines
medicine.symptom
Histamine
030215 immunology
Research Article
Zdroj: Journal of Diabetes Research
International Journal of Experimental Diabetes Research
International Journal of Experimental Diabetes Research, Hindawi Publishing Corporation, 2015, 2015, pp.965056. 〈10.1155/2015/965056〉
International Journal of Experimental Diabetes Research, Hindawi Publishing Corporation, 2015, 2015, pp.965056. ⟨10.1155/2015/965056⟩
International Journal of Experimental Diabetes Research, 2015, 2015, pp.965056. ⟨10.1155/2015/965056⟩
Journal of Diabetes Research, Vol 2015 (2015)
ISSN: 2314-6753
2314-6745
1560-4284
DOI: 10.1155/2015/965056〉
Popis: 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-γin 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.
Databáze: OpenAIRE
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