| First Author | Oulghazi S | Year | 2020 |
| Journal | Cells | Volume | 9 |
| Issue | 12 | PubMed ID | 33291571 |
| Mgi Jnum | J:302577 | Mgi Id | MGI:6508664 |
| Doi | 10.3390/cells9122597 | Citation | Oulghazi S, et al. (2020) Adaptive Immunity and Pathogenesis of Diabetes: Insights Provided by the alpha4-Integrin Deficient NOD Mouse. Cells 9(12):2597 |
| abstractText | 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 alpha4 integrin (CD49d) in other autoimmune diseases, we generated NOD mice with alpha4-deficient hematopoiesis (NOD.alpha4-/-) to study the role of alpha4 integrin in T1D. RESULTS: NOD.alpha4-/- mice developed islet-specific T-cells and antibodies, albeit quantitatively less than alpha4+ counterparts. Nevertheless, NOD.alpha4-/- mice were completely and life-long protected from diabetes and insulitis. Moreover, transplantation with isogeneic alpha4-/- bone marrow prevented progression to T1D of pre-diabetic NOD.alpha4+ mice despite significant pre-existing islet cell injury. Transfer of alpha4+/CD3+, but not alpha4+/CD4+ splenocytes from diabetic to NOD.alpha4-/- mice induced diabetes with short latency. Despite an only modest contribution of adoptively transferred alpha4+/CD3+ cells to peripheral blood, pancreas-infiltrating T-cells were exclusively graft derived, i.e., alpha4+. Microbiota of diabetes-resistant NOD.alpha4-/- and pre-diabetic NOD.alpha4+ mice were identical. Co- housed diabetic NOD.alpha4+ mice showed the characteristic diabetic dysbiosis, implying causality of diabetes for dysbiosis. Incidentally, NOD.alpha4-/- mice were protected from autoimmune sialitis. CONCLUSION: alpha4 is a potential target for primary or secondary prevention of T1D. |
