TY  - JOUR
A1  - Oulghazi, Salim
A1  - Wegner, Sarah Katharina
A1  - Spohn, Gabriele
A1  - Müller, Nina
A1  - Harenkamp, Sabine
A1  - Stenzinger, Albrecht
A1  - Papayannopoulou, Thalia
A1  - Bonig, Halvard-Björn
T1  - Adaptive immunity and pathogenesis of diabetes: insights provided by the α4–integrin deficient NOD mouse
T2  - Cells
N2  - 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.
KW  - VLA4
KW  - CD49d
KW  - type-1-diabetes
KW  - autoimmune diabetes
KW  - sialitis
KW  - integrin
Y1  - 2020
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/57475
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-574756
SN  - 2073-4409
VL  - 9
IS  - Article 2597
PB  - MDPI
CY  - Basel
ER  -