Show simple item record

dc.contributor.authorChen, Yi-Guang
dc.contributor.authorMordes, John P.
dc.contributor.authorBlankenhorn, Elizabeth P.
dc.contributor.authorKashmiri, Himala
dc.contributor.authorKaldunski, Mary L.
dc.contributor.authorJia, Shuang
dc.contributor.authorGeoffrey, Rhonda
dc.contributor.authorWang, Xujing
dc.contributor.authorHessner, Martin J.
dc.date2022-08-11T08:08:31.000
dc.date.accessioned2022-08-23T15:57:53Z
dc.date.available2022-08-23T15:57:53Z
dc.date.issued2013-09-01
dc.date.submitted2015-03-24
dc.identifier.citationGenes Immun. 2013 Sep;14(6):387-400. doi: 10.1038/gene.2013.31. Epub 2013 Jun 6. <a href="http://dx.doi.org/10.1038/gene.2013.31">Link to article on publisher's site</a>
dc.identifier.issn1466-4879 (Linking)
dc.identifier.doi10.1038/gene.2013.31
dc.identifier.pmid23739610
dc.identifier.urihttp://hdl.handle.net/20.500.14038/30303
dc.description.abstractThe dilute plasma cytokine milieu associated with type 1 diabetes (T1D), while difficult to measure directly, is sufficient to drive transcription in a bioassay that uses healthy leukocytes as reporters. Previously, we reported disease-associated, partially IL-1 dependent, transcriptional signatures in both T1D patients and the BioBreeding (BB) rat model. Here, we examine temporal signatures in congenic BBDR.lyp/lyp rats that develop spontaneous T1D, and BBDR rats where T1D progresses only after immunological perturbation in young animals. After weaning, the BBDR temporal signature showed early coincident induction of transcription related to innate inflammation as well as IL-10- and TGF-beta-mediated regulation. BBDR plasma cytokine levels mirrored the signatures showing early inflammation, followed by induction of a regulated state that correlated with failure of virus to induce T1D in older rats. In contrast, the BBDR.lyp/lyp temporal signature exhibited asynchronous dynamics, with delayed induction of inflammatory transcription and later, weaker induction of regulatory transcription, consistent with their deficiency in regulatory T cells. Through longitudinal analyses of plasma-induced signatures in BB rats and a human T1D progressor, we have identified changes in immunoregulatory processes that attenuate a preexisting innate inflammatory state in BBDR rats, suggesting a mechanism underlying the decline in T1D susceptibility with age.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=23739610&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4027975/
dc.subjectAge Factors
dc.subjectAnimals
dc.subjectDiabetes Mellitus, Type 1
dc.subject*Disease Resistance
dc.subjectHumans
dc.subjectInterleukin-10
dc.subjectParvovirus
dc.subjectRats
dc.subjectRats, Inbred Strains
dc.subject*Transcriptome
dc.subjectTransforming Growth Factor beta
dc.subjectEndocrinology, Diabetes, and Metabolism
dc.subjectImmunology and Infectious Disease
dc.titleTemporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced type 1 diabetes
dc.typeJournal Article
dc.source.journaltitleGenes and immunity
dc.source.volume14
dc.source.issue6
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/faculty_pubs/564
dc.identifier.contextkey6889227
html.description.abstract<p>The dilute plasma cytokine milieu associated with type 1 diabetes (T1D), while difficult to measure directly, is sufficient to drive transcription in a bioassay that uses healthy leukocytes as reporters. Previously, we reported disease-associated, partially IL-1 dependent, transcriptional signatures in both T1D patients and the BioBreeding (BB) rat model. Here, we examine temporal signatures in congenic BBDR.lyp/lyp rats that develop spontaneous T1D, and BBDR rats where T1D progresses only after immunological perturbation in young animals. After weaning, the BBDR temporal signature showed early coincident induction of transcription related to innate inflammation as well as IL-10- and TGF-beta-mediated regulation. BBDR plasma cytokine levels mirrored the signatures showing early inflammation, followed by induction of a regulated state that correlated with failure of virus to induce T1D in older rats. In contrast, the BBDR.lyp/lyp temporal signature exhibited asynchronous dynamics, with delayed induction of inflammatory transcription and later, weaker induction of regulatory transcription, consistent with their deficiency in regulatory T cells. Through longitudinal analyses of plasma-induced signatures in BB rats and a human T1D progressor, we have identified changes in immunoregulatory processes that attenuate a preexisting innate inflammatory state in BBDR rats, suggesting a mechanism underlying the decline in T1D susceptibility with age.</p>
dc.identifier.submissionpathfaculty_pubs/564
dc.contributor.departmentDepartment of Medicine
dc.source.pages387-400


This item appears in the following Collection(s)

Show simple item record