title: Histidine Decarboxylase Deficiency Prevents Autoimmune Diabetes in NOD Mice.
abstract: 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.
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8147, Hôpital Necker, 75015 Paris, France ; CNRS UMR 8104, Cochin Institute, 75014 Paris, France ; INSERM U1016, Cochin Institute, 75014 Paris, France ; Center of Excellence, LABEX Inflamex, 75014 Paris, France.
authors.forename: Manal
authors.initials: M
authors.lastname: Alkan
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8147, Hôpital Necker, 75015 Paris, France.
authors.forename: François
authors.initials: F
authors.lastname: Machavoine
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8147, Hôpital Necker, 75015 Paris, France.
authors.forename: Rachel
authors.initials: R
authors.lastname: Rignault
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8104, Cochin Institute, 75014 Paris, France ; INSERM U1016, Cochin Institute, 75014 Paris, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Dam
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8147, Hôpital Necker, 75015 Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Dy
authors.affiliation: Université Paris Descartes, 75014 Paris, France ; CNRS UMR 8147, Hôpital Necker, 75015 Paris, France ; CNRS UMR 8104, Cochin Institute, 75014 Paris, France ; INSERM U1016, Cochin Institute, 75014 Paris, France ; Center of Excellence, LABEX Inflamex, 75014 Paris, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thieblemont
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D006632:Histamine / Q000276:immunology*; D006640:Histidine Decarboxylase / Q000235:genetics*; D007371:Interferon-gamma / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D020738:Leptin / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD / Q000235:genetics* / Q000276:immunology; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D020738:Leptin; D018664:Interleukin-12; D006632:Histamine; D007371:Interferon-gamma; D006640:Histidine Decarboxylase