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研究揭示1型糖尿病患者体内β细胞特异性CD8 + T细胞的功能
2020-03-31 13:09

美国圣裘德儿童研究医院Ben Youngblood研究小组的最新研究探明了在1型糖尿病(T1D)患者中,β细胞特异性CD8 + T细胞维持了与干细胞记忆相关的表观遗传基序。相关论文于2020年3月30日在线发表在国际学术期刊《自然-免疫学》杂志上。

为了研究β细胞特异性CD8 + T细胞的长期存活特性,研究人员建立了基于DNA甲基化的T细胞“多能指数”,并发现β细胞特异性CD8 + T细胞保留了其干性表观遗传多能性。使用测序对转座酶可接近的染色质进行单细胞测定,研究人员证实了单个β细胞特异性CD8 + T细胞中原始以及与效应子相关的表观遗传基序共存。

对β细胞特异性CD8 + T细胞解剖分布的测定和干性相关表观遗传基序的建立表明,与从小鼠胰腺中分离出的自身反应性CD8 + T细胞相比,从淋巴组织中分离出的相同细胞保留了其发育可塑性和表观遗传特征。总的来说,这些数据为β细胞特异性CD8 + T细胞应答的长期性提供了新的见解,并证实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。

据悉,1型糖尿病中的β细胞特异性CD8 + T细胞尽管具有恒定的抗原来源,但仍具有针对自生组织反应的潜能。

附:英文原文

Title: Beta cell-specific CD8 + T cells maintain stem cell memory-associated epigenetic programs during type 1 diabetes

Author: Hossam A. Abdelsamed, Caitlin C. Zebley, Hai Nguyen, Rachel L. Rutishauser, Yiping Fan, Hazem E. Ghoneim, Jeremy Chase Crawford, Francesca Alfei, Shanta Alli, Susan Pereira Ribeiro, Ashley H. Castellaw, Maureen A. McGargill, Hongjian Jin, Shannon K. Boi, Cate Speake, Elisavet Serti, Laurence A. Turka, Michael E. Busch, Mars Stone, Steven G. Deeks, Rafick-Pierre Sekaly, Dietmar Zehn, Eddie A. James, Gerald T. Nepom, Ben Youngblood

Issue&Volume: 2020-03-30

Abstract: 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.

DOI: 10.1038/s41590-020-0633-5

Source: https://www.nature.com/articles/s41590-020-0633-5

Nature Immunology:《自然—免疫学》,创刊于2000年。隶属于施普林格·自然出版集团,最新IF:31.25
官方网址:https://www.nature.com/ni/
投稿链接:https://mts-ni.nature.com/cgi-bin/main.plex


本期文章:《自然—免疫学》:Online/在线发表

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