| First Author | Bobbala D | Year | 2012 |
| Journal | Diabetologia | Volume | 55 |
| Issue | 11 | Pages | 3010-20 |
| PubMed ID | 22890824 | Mgi Jnum | J:191833 |
| Mgi Id | MGI:5463177 | Doi | 10.1007/s00125-012-2675-1 |
| Citation | Bobbala D, et al. (2012) Interleukin-15 plays an essential role in the pathogenesis of autoimmune diabetes in the NOD mouse. Diabetologia 55(11):3010-20 |
| abstractText | AIMS/HYPOTHESIS: IL-15, induced by innate immune stimuli, promotes rheumatoid arthritis and inflammatory bowel disease. However, its role in autoimmune type 1 diabetes is unclear. Our aim is to define the role of IL-15 in the pathogenesis of diabetes in the NOD mouse model. METHODS: We generated NOD.Il15(-/-) mice expressing a polyclonal repertoire of T cell antigen receptor (TCR) or a transgenic TCR and monitored diabetes onset and insulitis. NOD Scid.Il15(-/-) (full name NOD.CB17-Prkdc (scid)/NCrCrl) and NOD Scid.gamma (full name NOD.Cg-Prkdc(scid) Il2rg ( tm1Wjl )/SzJ) mice were used to distinguish the requirement for IL-15 signalling in CD8(+) T cells and antigen-presenting cells (APCs) to induce disease. We examined the effect of blocking IL-15 signalling on diabetes onset in NOD mice. RESULTS: At 7 months of age, more than 75% of the NOD Il15(-/-) female mice remained diabetes free compared with only 30% in the control group. Diabetes incidence was also decreased in 8.3-NOD (full name NOD Cg-Tg[TcraTcrbNY8.3]-1Pesa/DvsJ).Il15(-/-) mice expressing a highly pathogenic transgenic TCR on CD8(+) T cells. Adoptive transfer of splenocytes from diabetic NOD and 8.3-NOD donors induced disease in NOD Scid recipients but not in NOD Scid.Il15(-/-) or NOD Scid.gamma mice. Transient blockade of IL-15 signalling at the onset of insulitis prevented diabetes in NOD mice. CONCLUSIONS/INTERPRETATION: Our results show that IL-15 is needed for the initial activation of diabetogenic CD8(+) T cells as well as for sustaining the diabetogenic potential of antigen-stimulated cells, acting on both CD8(+) T cells and on APCs. Our findings demonstrate a critical role for IL-15 in the pathogenesis of autoimmune diabetes and suggest that IL-15 is a promising therapeutic target. |
