Bridge between type 1 diabetes in mouse and man

Abstract

Type 1 diabetes (T1D) manifested with hyperglycemia is an autoimmune disease resulting from destruction of insulin-producing pancreatic β cells (1, 2). The nonobese diabetic (NOD) mouse is the preclinical model closest to T1D in man and has provided an invaluable understanding of basic immune pathogenesis, genetic and environmental risk factors, and immune-targeting strategies (3). However, investigators observed that histopathology in T1D patients differs significantly from that in NOD mice (4), and therapies developed with NOD mice are not easily directly translated into treating T1D patients (5). Due to ethical issues, much research on pathogenesis and therapies cannot be directly performed in T1D patients. Therefore, investigators have been attempting to develop humanized mouse models to better mimic pathogenesis and therapy in T1D patients. Humanized mice are generally defined as immunodeficient mice engrafted with human hematopoietic cells or tissues or mice that transgenically express human genes (6). In PNAS, Tan et al. (7) combined these two approaches and developed a new humanized model of T1D. T1D pathogenesis in both NOD mice and humans is associated with a particular MHC haplotype (designated H2 in mice and HLA in humans), H2-IAg7 with H2-KdDb in NOD mice (8⇓–10) and HLA-DQ8 or DR4 with HLA-A2 in humans (11, 12). In NOD mice, T1D is mediated by both autoreactive CD4+ and CD8+ T cells in collaboration with B cells and innate immune cells (3). Autoreactive CD4+ T cells in T1D recognize a variety of autoantigens … [↵][1]1Email: dzeng{at}coh.org. [1]: #xref-corresp-1-1