title: Type 1 diabetes in NOD mice unaffected by mast cell deficiency.
abstract: Mast cells have been invoked as important players in immune responses associated with autoimmune diseases. Based on in vitro studies, or in vivo through the use of Kit mutant mice, mast cells have been suggested to play immunological roles in direct antigen presentation to both CD4(+) and CD8(+) T cells, in the regulation of T-cell and dendritic cell migration to lymph nodes, and in Th1 versus Th2 polarization, all of which could significantly impact the immune response against self-antigens in autoimmune disease, including type 1 diabetes (T1D). Until now, the role of mast cells in the onset and incidence of T1D has only been indirectly tested through the use of low-specificity mast cell inhibitors and activators, and published studies reported contrasting results. Our three laboratories have generated independently two strains of mast cell-deficient nonobese diabetic (NOD) mice, NOD.Cpa3(Cre/+) (Heidelberg) and NOD.Kit(W-sh/W-sh) (Leuven and Boston), to address the effects of mast cell deficiency on the development of T1D in the NOD strain. Our collective data demonstrate that both incidence and progression of T1D in NOD mice are independent of mast cells. Moreover, analysis of pancreatic lymph node cells indicated that lack of mast cells has no discernible effect on the autoimmune response, which involves both innate and adaptive immune components. Our results demonstrate that mast cells are not involved in T1D in the NOD strain, making their role in this process nonessential and excluding them as potential therapeutic targets.
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Dario A
authors.initials: DA
authors.lastname: Gutierrez
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA.
authors.forename: Wenxian
authors.initials: W
authors.lastname: Fu
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Susann
authors.initials: S
authors.lastname: Schonefeldt
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Thorsten B
authors.initials: TB
authors.lastname: Feyerabend
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Ortiz-Lopez
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Lampi
authors.affiliation: Autoimmune Genetics Laboratory, VIB, Leuven, Belgium Department of Microbiology and Immunology, University of Leuven, Leuven, Belgium hr.rodewald@dkfz.de diane_mathis@hms.harvard.edu adrian.liston@vib.be.
authors.forename: Adrian
authors.initials: A
authors.lastname: Liston
authors.affiliation: Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA hr.rodewald@dkfz.de diane_mathis@hms.harvard.edu adrian.liston@vib.be.
authors.forename: Diane
authors.initials: D
authors.lastname: Mathis
authors.affiliation: Division of Cellular Immunology, German Cancer Research Center, Heidelberg, Germany hr.rodewald@dkfz.de diane_mathis@hms.harvard.edu adrian.liston@vib.be.
authors.forename: Hans-Reimer
authors.initials: HR
authors.lastname: Rodewald
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D043422:Carboxypeptidases A / Q000235:genetics / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D005260:Female; D008297:Male; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD
chemical_list: D043422:Carboxypeptidases A; C503326:Cpa3 protein, mouse