| First Author | Yong J | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 4269 |
| PubMed ID | 30862859 | Mgi Jnum | J:275879 |
| Mgi Id | MGI:6307177 | Doi | 10.1038/s41598-019-38905-z |
| Citation | Yong J, et al. (2019) Increased risk for T cell autoreactivity to ss-cell antigens in the mice expressing the A(vy) obesity-associated gene. Sci Rep 9(1):4269 |
| abstractText | There has been considerable debate as to whether obesity can act as an accelerator of type 1 diabetes (T1D). We assessed this possibility using transgenic mice (MIP-TF mice) whose ss-cells express enhanced green fluorescent protein (EGFP). Infecting these mice with EGFP-expressing murine herpes virus-68 (MHV68-EGFP) caused occasional transient elevation in their blood glucose, peri-insulitis, and Th1 responses to EGFP which did not spread to other ss-cell antigens. We hypothesized that obesity-related systemic inflammation and ss-cell stress could exacerbate the MHV68-EGFP-induced ss-cell autoreactivity. We crossed MIP-TF mice with A(vy) mice which develop obesity and provide models of metabolic disease alongside early stage T2D. Unlike their MIP-TF littermates, MHV68-EGFP-infected A(vy)/MIP-TF mice developed moderate intra-insulitis and transient hyperglycemia. MHV68-EGFP infection induced a more pronounced intra-insulitis in older, more obese, A(vy)/MIP-TF mice. Moreover, in MHV68-EGFP-infected A(vy)/MIP-TF mice, Th1 reactivity spread from EGFP to other ss-cell antigens. Thus, the spreading of autoreactivity among ss-cell antigens corresponded with the transition from peri-insulitis to intra-insulitis and occurred in obese A(vy)/MIP-TF mice but not lean MIP-TF mice. These observations are consistent with the notion that obesity-associated systemic inflammation and ss-cell stress lowers the threshold necessary for T cell autoreactivity to spread from EGFP to other ss-cell autoantigens. |
