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- Publisher Website: 10.1038/s41598-019-38905-z
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- PMID: 30862859
- WOS: WOS:000460924100009
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Article: Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the Avy obesity-associated gene
Title | Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the A<sup>vy</sup> obesity-associated gene |
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Authors | |
Issue Date | 2019 |
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 Identifier | http://hdl.handle.net/10722/285836 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Yong, Jing | - |
dc.contributor.author | Tian, Jide | - |
dc.contributor.author | Dang, Hoa | - |
dc.contributor.author | Wu, Ting Ting | - |
dc.contributor.author | Atkinson, Mark A. | - |
dc.contributor.author | Sun, Ren | - |
dc.contributor.author | Kaufman, Daniel L. | - |
dc.date.accessioned | 2020-08-18T04:56:46Z | - |
dc.date.available | 2020-08-18T04:56:46Z | - |
dc.date.issued | 2019 | - |
dc.identifier.citation | Scientific Reports, 2019, v. 9, n. 1, article no. 4269 | - |
dc.identifier.uri | http://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.language | eng | - |
dc.relation.ispartof | Scientific Reports | - |
dc.rights | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. | - |
dc.title | Increased risk for T cell autoreactivity to ß-cell antigens in the mice expressing the A<sup>vy</sup> obesity-associated gene | - |
dc.type | Article | - |
dc.description.nature | published_or_final_version | - |
dc.identifier.doi | 10.1038/s41598-019-38905-z | - |
dc.identifier.pmid | 30862859 | - |
dc.identifier.pmcid | PMC6414670 | - |
dc.identifier.scopus | eid_2-s2.0-85062875478 | - |
dc.identifier.volume | 9 | - |
dc.identifier.issue | 1 | - |
dc.identifier.spage | article no. 4269 | - |
dc.identifier.epage | article no. 4269 | - |
dc.identifier.eissn | 2045-2322 | - |
dc.identifier.isi | WOS:000460924100009 | - |
dc.identifier.issnl | 2045-2322 | - |