Adaptive immunity and pathogenesis of diabetes: insights provided by the α4-integrin deficient NOD mouse
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 i...
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| Hauptverfasser: | , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
4 December 2020
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| In: |
Cells
Year: 2020, Jahrgang: 9, Heft: 12, Pages: 1-16 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9122597 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cells9122597 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2073-4409/9/12/2597 
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| Verfasserangaben: | Salim Oulghazi, Sarah K. Wegner, Gabriele Spohn, Nina Müller, Sabine Harenkamp, Albrecht Stenzinger, Thalia Papayannopoulou and Halvard Bonig |
| Zusammenfassung: | 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. |
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| Beschreibung: | Gesehen am 08.02.2022 |
| Beschreibung: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells9122597 |