Dataset Information

Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the ?4-Integrin Deficient NOD Mouse.

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 ?4 integrin (CD49d) in other autoimmune diseases, we generated NOD mice with ?4-deficient hematopoiesis (NOD.?4-/-) to study the role of ?4 integrin in T1D.

Results

NOD.?4-/- mice developed islet-specific T-cells and antibodies, albeit quantitatively less than ?4+ counterparts. Nevertheless, NOD.?4-/- mice were completely and life-long protected from diabetes and insulitis. Moreover, transplantation with isogeneic ?4-/- bone marrow prevented progression to T1D of pre-diabetic NOD.?4+ mice despite significant pre-existing islet cell injury. Transfer of ?4+/CD3+, but not ?4+/CD4+ splenocytes from diabetic to NOD.?4-/- mice induced diabetes with short latency. Despite an only modest contribution of adoptively transferred ?4+/CD3+ cells to peripheral blood, pancreas-infiltrating T-cells were exclusively graft derived, i.e., ?4+. Microbiota of diabetes-resistant NOD.?4-/- and pre-diabetic NOD.?4+ mice were identical. Co- housed diabetic NOD.?4+ mice showed the characteristic diabetic dysbiosis, implying causality of diabetes for dysbiosis. Incidentally, NOD.?4-/- mice were protected from autoimmune sialitis.

Conclusion

?4 is a potential target for primary or secondary prevention of T1D.

SUBMITTER: Oulghazi S

PROVIDER: S-EPMC7761835 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the α4-Integrin Deficient NOD Mouse.

Oulghazi Salim S Wegner Sarah K SK Spohn Gabriele G Müller Nina N Harenkamp Sabine S Stenzinger Albrecht A Papayannopoulou Thalia T Bonig Halvard H

Cells 20201204 12

<h4>Background</h4>The spontaneously diabetic "non-obese diabetic" (NOD) mouse is a faithful model of human type-1 diabetes (T1D).<h4>Methods</h4>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.<h4>Results</h4>NOD.α4-/- mice developed islet-specific T-cells and antibodies, albeit quantitatively less than α4+ counterparts. Nevertheless, NOD.α4-/- mice were complete ...[more]

PMID: 33291571

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