title: β Cells that Resist Immunological Attack Develop during Progression of Autoimmune Diabetes in NOD Mice.
abstract: Type 1 diabetes (T1D) is a chronic autoimmune disease that involves immune-mediated destruction of β cells. How β cells respond to immune attack is unknown. We identified a population of β cells during the progression of T1D in non-obese diabetic (NOD) mice that survives immune attack. This population develops from normal β cells confronted with islet infiltrates. Pathways involving cell movement, growth and proliferation, immune responses, and cell death and survival are activated in these cells. There is reduced expression of β cell identity genes and diabetes antigens and increased immune inhibitory markers and stemness genes. This new subpopulation is resistant to killing when diabetes is precipitated with cyclophosphamide. Human β cells show similar changes when cultured with immune cells. These changes may account for the chronicity of the disease and the long-term survival of β cells in some patients.
authors.affiliation: Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
authors.forename: Jinxiu
authors.initials: J
authors.lastname: Rui
authors.affiliation: Department of Immunobiology, Yale University, New Haven, CT 06520, USA.
authors.forename: Songyan
authors.initials: S
authors.lastname: Deng
authors.affiliation: Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, MA 02142, USA.
authors.forename: Arnon
authors.initials: A
authors.lastname: Arazi
authors.affiliation: Department of Internal Medicine, Yale University, New Haven, CT 06520, USA.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Perdigoto
authors.affiliation: Department of Pathology, Yale University, New Haven, CT 06520, USA.
authors.forename: Zongzhi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Immunobiology, Yale University, New Haven, CT 06520, USA; Department of Internal Medicine, Yale University, New Haven, CT 06520, USA. Electronic address: kevan.herold@yale.edu.
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017252:CD3 Complex / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007167:Immunotherapy; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000276:immunology* / Q000473:pathology*; D008214:Lymphocytes / Q000187:drug effects / Q000473:pathology; D016688:Mice, Inbred NOD; D060888:Real-Time Polymerase Chain Reaction; D017423:Sequence Analysis, RNA; D014158:Transcription, Genetic / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D017252:CD3 Complex
keywords: autoimmunity; immune regulation; stem cell; β cell