title: A minor subset of Batf3-dependent antigen-presenting cells in islets of Langerhans is essential for the development of autoimmune diabetes.
abstract: Autoimmune diabetes is characterized by inflammatory infiltration; however, the initiating events are poorly understood. We found that the islets of Langerhans in young nonobese diabetic (NOD) mice contained two antigen-presenting cell (APC) populations: a major macrophage and a minor CD103(+) dendritic cell (DC) population. By 4 weeks of age, CD4(+) T cells entered islets coincident with an increase in CD103(+) DCs. In order to examine the role of the CD103(+) DCs in diabetes, we examined Batf3-deficient NOD mice that lacked the CD103(+) DCs in islets and pancreatic lymph nodes. This led to a lack of autoreactive T cells in islets and, importantly, no incidence of diabetes. Additional examination revealed that presentation of major histocompatibility complex (MHC) class I epitopes in the pancreatic lymph nodes was absent with a partial impairment of MHC class II presentation. Altogether, this study reveals that CD103(+) DCs are essential for autoimmune diabetes development.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Ferris
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Carrero
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Mohan
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Calderon
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: unanue@wustl.edu.
authors.forename: Emil R
authors.initials: ER
authors.lastname: Unanue
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis*; D015551:Autoimmunity / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics*; D016827:CD8 Antigens / Q000096:biosynthesis*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D000939:Epitopes / Q000096:biosynthesis / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis / Q000276:immunology; D018398:Homeodomain Proteins / Q000235:genetics; D007249:Inflammation / Q000276:immunology; D039001:Integrin alpha Chains / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000166:cytology / Q000276:immunology; D007801:Langerhans Cells / Q000276:immunology*; D008198:Lymph Nodes / Q000166:cytology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D010179:Pancreas / Q000166:cytology; D012097:Repressor Proteins / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D016827:CD8 Antigens; C431698:CD8alpha antigen; D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D018398:Homeodomain Proteins; D039001:Integrin alpha Chains; D012097:Repressor Proteins; C533289:SNFT protein, mouse; C091367:alpha E integrins; C064658:RAG-1 protein