Autoimmunity triggers in the NOD mouse: a role for natural auto-antibody reactivities in type 1 diabetes.
The nonobese diabetic mouse (NOD) is widely used as a model to study human type 1 diabetes (T1D). In the NOD mouse T1D is a T cell-mediated autoimmune disease of complex etiology in which B cells play an essential role. One of the major unresolved issues in T1D is the genetic and/or environmental factors that trigger the autoimmune reaction. In the NOD mouse, as in humans, auto-antibodies to pancreatic islets are present at early ages and are highly correlated to diabetes progression, but their etiological role has long been disputed. NOD auto-antibodies have the characteristics of a natural repertoire, and B1 cells, the main natural antibody producers, exhibit functional differences in this strain that could have consequences for disease determination. Using a genetic approach, we propose to test if the NOD natural auto-antibody repertoire includes innate reactivities that participate in diabetes pathogenesis by promoting insulitis initiation.
Côrte-Real
Joana
J
Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Duarte
Nádia
N
Tavares
Luís
L
Penha-Gonçalves
Carlos
C
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D018448:Models, Immunological; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D001323:Autoantibodies; D001324:Autoantigens; D007075:Immunoglobulin M