File Download
  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene

TitleIncreased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the A<sup>vy</sup> obesity-associated gene
Authors
Issue Date2019
Citation
Scientific Reports, 2019, v. 9, n. 1, article no. 4269 How to Cite?
Abstract© 2019, The Author(s). 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.
Persistent Identifierhttp://hdl.handle.net/10722/285836
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorYong, Jing-
dc.contributor.authorTian, Jide-
dc.contributor.authorDang, Hoa-
dc.contributor.authorWu, Ting Ting-
dc.contributor.authorAtkinson, Mark A.-
dc.contributor.authorSun, Ren-
dc.contributor.authorKaufman, Daniel L.-
dc.date.accessioned2020-08-18T04:56:46Z-
dc.date.available2020-08-18T04:56:46Z-
dc.date.issued2019-
dc.identifier.citationScientific Reports, 2019, v. 9, n. 1, article no. 4269-
dc.identifier.urihttp://hdl.handle.net/10722/285836-
dc.description.abstract© 2019, The Author(s). 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.-
dc.languageeng-
dc.relation.ispartofScientific Reports-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleIncreased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the A<sup>vy</sup> obesity-associated gene-
dc.typeArticle-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41598-019-38905-z-
dc.identifier.pmid30862859-
dc.identifier.pmcidPMC6414670-
dc.identifier.scopuseid_2-s2.0-85062875478-
dc.identifier.volume9-
dc.identifier.issue1-
dc.identifier.spagearticle no. 4269-
dc.identifier.epagearticle no. 4269-
dc.identifier.eissn2045-2322-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats