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Publication
Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the
a4-Integrin Deficient NOD Mouse.
Authors Oulghazi S, Wegner SK, Spohn G, Müller N, Harenkamp S, Stenzinger A,
Papayannopoulou T, Bonig H
Submitted By Halvard Bonig on 2/22/2021
Status Published
Journal Cells
Year 2020
Date Published 12/4/2020
Volume : Pages 9 : Not Specified
PubMed Reference 33291571
Abstract The spontaneously diabetic "non-obese diabetic" (NOD) mouse is a faithful model
of human type-1 diabetes (T1D)., Given the pivotal role of a4 integrin (CD49d)
in other autoimmune diseases, we generated NOD mice with a4-deficient
hematopoiesis (NOD.a4-/-) to study the role of a4 integrin in T1D., NOD.a4-/-
mice developed islet-specific T-cells and antibodies, albeit quantitatively less
than a4+ counterparts. Nevertheless, NOD.a4-/- mice were completely and
life-long protected from diabetes and insulitis. Moreover, transplantation with
isogeneic a4-/- bone marrow prevented progression to T1D of pre-diabetic NOD.a4+
mice despite significant pre-existing islet cell injury. Transfer of a4+/CD3+,
but not a4+/CD4+ splenocytes from diabetic to NOD.a4-/- mice induced diabetes
with short latency. Despite an only modest contribution of adoptively
transferred a4+/CD3+ cells to peripheral blood, pancreas-infiltrating T-cells
were exclusively graft derived, i.e., a4+. Microbiota of diabetes-resistant
NOD.a4-/- and pre-diabetic NOD.a4+ mice were identical. Co- housed diabetic
NOD.a4+ mice showed the characteristic diabetic dysbiosis, implying causality of
diabetes for dysbiosis. Incidentally, NOD.a4-/- mice were protected from
autoimmune sialitis., a4 is a potential target for primary or secondary
prevention of T1D.




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