Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes.,Nature Immunology

当前位置： X-MOL 学术 › Nat. Immunol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Beta cell-specific CD8+ T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes.
Nature Immunology ( IF 27.7 ) Pub Date : 2020-03-30 , DOI: 10.1038/s41590-020-0633-5
Hossam A Abdelsamed _{1,

2} , Caitlin C Zebley _{1,

3} , Hai Nguyen ₄ , Rachel L Rutishauser ₅ , Yiping Fan ₆ , Hazem E Ghoneim _{1,

7} , Jeremy Chase Crawford ₁ , Francesca Alfei ₈ , Shanta Alli ₁ , Susan Pereira Ribeiro ₉ , Ashley H Castellaw ₁ , Maureen A McGargill ₁ , Hongjian Jin ₆ , Shannon K Boi ₁ , Cate Speake ₁₀ , Elisavet Serti ₁₁ , Laurence A Turka _{11,

12} , Michael E Busch ₁₃ , Mars Stone ₁₃ , Steven G Deeks ₅ , Rafick-Pierre Sekaly ₉ , Dietmar Zehn ₈ , Eddie A James ₄ , Gerald T Nepom _{4,

11} , Ben Youngblood _{1,

3}

Affiliation

Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Surgery, Thomas E. Starzl Transplantation Institute, University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA.
Graduate School of Biomedical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Translational Research Program, Benaroya Research Institute, Seattle, WA, USA.
Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Center for Applied Bioinformatics, St. Jude Children's Research Hospital, Memphis, TN, USA.
Department of Microbial Infection and Immunity, College of Medicine, The Ohio State University, Columbus, OH, USA.
Division of Animal Physiology and Immunology, School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany.
Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.
Diabetes Research Program, Benaroya Research Institute, Seattle, WA, USA.
Immune Tolerance Network, Bethesda, MD, USA.
Center for Translational Sciences, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Vitalant Research Institute, San Francisco, CA, USA.

The pool of beta cell-specific CD8+ T cells in type 1 diabetes (T1D) sustains an autoreactive potential despite having access to a constant source of antigen. To investigate the long-lived nature of these cells, we established a DNA methylation-based T cell 'multipotency index' and found that beta cell-specific CD8+ T cells retained a stem-like epigenetic multipotency score. Single-cell assay for transposase-accessible chromatin using sequencing confirmed the coexistence of naive and effector-associated epigenetic programs in individual beta cell-specific CD8+ T cells. Assessment of beta cell-specific CD8+ T cell anatomical distribution and the establishment of stem-associated epigenetic programs revealed that self-reactive CD8+ T cells isolated from murine lymphoid tissue retained developmentally plastic phenotypic and epigenetic profiles relative to the same cells isolated from the pancreas. Collectively, these data provide new insight into the longevity of beta cell-specific CD8+ T cell responses and document the use of this methylation-based multipotency index for investigating human and mouse CD8+ T cell differentiation.

中文翻译：

在1型糖尿病期间，β细胞特异性CD8 + T细胞维持与干细胞记忆相关的表观遗传程序。

1型糖尿病（T1D）中的β细胞特异性CD8 + T细胞库尽管具有恒定的抗原来源，但仍具有自身反应潜力。为了研究这些细胞的长寿性质，我们建立了基于DNA甲基化的T细胞“多能指数”，并发现β细胞特异性CD8 + T细胞保留了干样表观遗传多能得分。使用测序的转座酶可及染色质的单细胞测定法证实了单个β细胞特异性CD8 + T细胞中幼稚和与效应子相关的表观遗传程序的共存。对β细胞特异性CD8 + T细胞解剖分布的评估和干相关表观遗传程序的建立表明，从鼠淋巴组织中分离出的自反应性CD8 + T细胞相对于从胰腺中分离出的同一细胞保留了发育上的可塑性表型和表观遗传学特征。总的来说，这些数据为β细胞特异性CD8 + T细胞应答的寿命提供了新的见识，并证明了这种基于甲基化的多能指数在研究人类和小鼠CD8 + T细胞分化中的用途。

更新日期：2020-04-24

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11