小柯机器人

瑞士苏黎世大学Burkhard Becher研究小组揭示多发性硬化症存在非遗传性免疫紊乱。相关论文于2022年2月16日在线发表在《自然》杂志上。

Author: Ingelfinger, Florian, Gerdes, Lisa Ann, Kavaka, Vladyslav, Krishnarajah, Sinduya, Friebel, Ekaterina, Galli, Edoardo, Zwicky, Pascale, Furrer, Reinhard, Peukert, Christian, Dutertre, Charles-Antoine, Eglseer, Klara Magdalena, Ginhoux, Florent, Flierl-Hecht, Andrea, Kmpfel, Tania, De Feo, Donatella, Schreiner, Bettina, Mundt, Sarah, Kerschensteiner, Martin, Hohlfeld, Reinhard, Beltrn, Eduardo, Becher, Burkhard

Issue&Volume: 2022-02-16

Abstract: Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions1,2. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25–IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.

DOI: 10.1038/s41586-022-04419-4

Source: https://www.nature.com/articles/s41586-022-04419-4

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
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