气候变化领域集成服务门户(CCPortal): T-cell responses to hybrid insulin peptides prior to type 1 diabetes development

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DOI	10.1073/pnas.2019129118
	T-cell responses to hybrid insulin peptides prior to type 1 diabetes development
	Mitchell A.M.; Alkanani A.A.; McDaniel K.A.; Pyle L.; Waugh K.; Steck A.K.; Nakayama M.; Yu L.; Gottlieb P.A.; Rewers M.J.; Michels A.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:6
英文摘要	T-cell responses to posttranslationally modified self-antigens are associated with many autoimmune disorders. In type 1 diabetes, hybrid insulin peptides (HIPs) are implicated in the T-cell-mediated destruction of insulin-producing β-cells within pancreatic islets. The natural history of the disease is such that it allows for the study of T-cell reactivity prior to the onset of clinical symptoms. We hypothesized that CD4 T-cell responses to posttranslationally modified islet peptides precedes diabetes onset. In a cohort of genetically at-risk individuals, we measured longitudinal T-cell responses to native insulin and hybrid insulin peptides. Both proinflammatory (interferon-γ) and antiinflammatory (interluekin-10) cytokine responses to HIPs were more robust than those to native peptides, and the ratio of such responses oscillated between pro- and antiinflammatory over time. However, individuals who developed islet autoantibodies or progressed to clinical type 1 diabetes had predominantly inflammatory T-cell responses to HIPs. Additionally, several HIP T-cell responses correlated to worsening measurements of blood glucose, highlighting the relevance of T-cell responses to posttranslationally modified peptides prior to autoimmune disease development. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Antigen; Autoimmunity; Posttranslational modification; T cell; Type 1 diabetes
语种	英语
scopus关键词	autoantibody; gamma interferon; glucose; hybrid insulin peptide; insulin; interleukin 10; peptide hormone; unclassified drug; adolescent; adult; Article; autoimmunity; child; cohort analysis; cytokine response; disease exacerbation; female; genetic risk; glucose blood level; human; human cell; immune response; inflammation; insulin dependent diabetes mellitus; major clinical study; male; pancreas islet; priority journal; protein processing; T lymphocyte
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/180675
作者单位	Barbara Davis Center for Diabetes, University of Colorado, Aurora, CO 80045, United States
推荐引用方式 GB/T 7714	Mitchell A.M.,Alkanani A.A.,McDaniel K.A.,et al. T-cell responses to hybrid insulin peptides prior to type 1 diabetes development[J],2021,118(6).
APA	Mitchell A.M..,Alkanani A.A..,McDaniel K.A..,Pyle L..,Waugh K..,...&Michels A.W..(2021).T-cell responses to hybrid insulin peptides prior to type 1 diabetes development.Proceedings of the National Academy of Sciences of the United States of America,118(6).
MLA	Mitchell A.M.,et al."T-cell responses to hybrid insulin peptides prior to type 1 diabetes development".Proceedings of the National Academy of Sciences of the United States of America 118.6(2021).