| First Author | Tan Q | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 8 | Pages | 2761-75 |
| PubMed ID | 24696448 | Mgi Jnum | J:229884 |
| Mgi Id | MGI:5754715 | Doi | 10.2337/db13-1504 |
| Citation | Tan Q, et al. (2014) IRAK-M deficiency promotes the development of type 1 diabetes in NOD mice. Diabetes 63(8):2761-75 |
| abstractText | Type 1 diabetes mellitus (T1DM) is an organ-specific autoimmune disease characterized by progressive destruction of insulin-secreting pancreatic beta-cells. Both T-cell-mediated adaptive responses as well as innate immune processes are involved in pathogenesis. Interleukin-1 receptor-associated kinase M (IRAK-M) can effectively inhibit the MyD88 downstream signals in Toll-like receptor pathways, while lack of IRAK-M is known to be associated with autoimmunity. Our study showed that IRAK-M-deficient (IRAK-M(-/-)) nonobese diabetic (NOD) mice displayed early onset and rapid progression of T1DM with impaired glucose tolerance, more severe insulitis, and increased serum anti-insulin autoantibodies. Mechanistic studies showed that the enhanced activation and antigen-presenting function of IRAK-M(-/-) antigen-presenting cells from IRAK-M(-/-) mice were responsible for the rapid progression of disease. Moreover, IRAK-M(-/-) dendritic cells induced enhanced activation of diabetogenic T cells in vitro and the rapid onset of T1DM in vivo in immunodeficient NOD mice when cotransferred with diabetogenic T cells. This study illustrates how the modulation of innate immune pathways through IRAK-M influences the development of autoimmune diabetes. |
