Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the α4-Integrin Deficient NOD Mouse.
Cells
; 9(12)2020 12 04.
Article
en En
| MEDLINE
| ID: mdl-33291571
ABSTRACT
BACKGROUND:
The spontaneously diabetic "non-obese diabetic" (NOD) mouse is a faithful model of human type-1 diabetes (T1D).METHODS:
Given the pivotal role of α4 integrin (CD49d) in other autoimmune diseases, we generated NOD mice with α4-deficient hematopoiesis (NOD.α4-/-) to study the role of α4 integrin in T1D.RESULTS:
NOD.α4-/- mice developed islet-specific T-cells and antibodies, albeit quantitatively less than α4+ counterparts. Nevertheless, NOD.α4-/- mice were completely and life-long protected from diabetes and insulitis. Moreover, transplantation with isogeneic α4-/- bone marrow prevented progression to T1D of pre-diabetic NOD.α4+ mice despite significant pre-existing islet cell injury. Transfer of α4+/CD3+, but not α4+/CD4+ splenocytes from diabetic to NOD.α4-/- mice induced diabetes with short latency. Despite an only modest contribution of adoptively transferred α4+/CD3+ cells to peripheral blood, pancreas-infiltrating T-cells were exclusively graft derived, i.e., α4+. Microbiota of diabetes-resistant NOD.α4-/- and pre-diabetic NOD.α4+ mice were identical. Co- housed diabetic NOD.α4+ mice showed the characteristic diabetic dysbiosis, implying causality of diabetes for dysbiosis. Incidentally, NOD.α4-/- mice were protected from autoimmune sialitis.CONCLUSION:
α4 is a potential target for primary or secondary prevention of T1D.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Integrina alfa4
/
Inmunidad Adaptativa
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Año:
2020
Tipo del documento:
Article