Journal article
Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced Type 1 Diabetes
Genes and immunity, v 14(6), pp 387-400
Sep 2013
PMID: 23739610
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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.
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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-β-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.
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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.
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Details
- Title
- Temporal induction of immunoregulatory processes coincides with age-dependent resistance to viral-induced Type 1 Diabetes
- Creators
- Yi-Guang Chen - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USAJohn P Mordes - Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAElizabeth P Blankenhorn - Department of Microbiology and Immunology, Drexel University College of Medicine, Philadelphia, PA, 35294, USAHimala Kashmiri - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USAMary L Kaldunski - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USAShuang Jia - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USARhonda Geoffrey - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USAXujing Wang - The Department of Physics, The Comprehensive Diabetes Center, The University of Alabama-Birmingham, Birmingham, AL, 35294, USAMartin J Hessner - The Max McGee National Research Center for Juvenile Diabetes, Children's Research Institute of the Children's Hospital of Wisconsin, and Department of Pediatrics at the Medical College of Wisconsin Milwaukee, WI 53226, USA
- Publication Details
- Genes and immunity, v 14(6), pp 387-400
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- [Retired Faculty]
- Web of Science ID
- WOS:000324099900006
- Scopus ID
- 2-s2.0-84883880468
- Other Identifier
- 991014877790804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Genetics & Heredity
- Immunology