以色列魏茨曼科学研究所Jakub Abramson等研究人员合作发现，胸腺模拟细胞可超越自我耐受性来工作。相关论文于2023年9月6日在线发表于国际学术期刊《自然》。
研究人员表示，胸腺中免疫能力强的T细胞是有效抵御各类病原体（包括病毒、细菌和真菌）的必要条件。胸腺上皮细胞（TEC）在这些过程中发挥着不可或缺的作用，以前的研究表明这些细胞具有显著的异质性。
研究人员利用多组学分析进一步了解了小鼠TEC的功能和发育多样性，并根据细胞转录状态和染色质图谱揭示了TEC区的详细图谱。分析结果突显了与功能明确的实质细胞群（包括内分泌细胞、微褶细胞和肌细胞）相似的非常规TEC亚群。通过聚焦内分泌和微褶TEC群体，研究人员发现内分泌TEC的发育需要Insm1，并且对以生长激素释放肽依赖方式维持胸腺细胞性至关重要；相比之下，微褶TEC的发育需要Spib，并且对胸腺IgA+浆细胞的生成至关重要。
总之，这项研究揭示了髓质TEC具有分化成各种类型的分子不同、功能明确的细胞的潜力，它们不仅有助于诱导中枢耐受性，还能调节胸腺其他驻留群体的稳态。
附：英文原文
Title: Thymic mimetic cells function beyond self-tolerance
Author: Givony, Tal, Leshkowitz, Dena, Del Castillo, Diana, Nevo, Shir, Kadouri, Noam, Dassa, Bareket, Gruper, Yael, Khalaila, Razi, Ben-Nun, Osher, Gome, Tom, Dobe, Jan, Ben-Dor, Shifra, Kedmi, Merav, Keren-Shaul, Hadas, Heffner-Krausz, Rebecca, Porat, Ziv, Golani, Ofra, Addadi, Yoseph, Brenner, Ori, Lo, David D., Goldfarb, Yael, Abramson, Jakub
Issue&Volume: 2023-09-06
Abstract: Development of immunocompetent T cells in the thymus is required for effective defence against all types of pathogens, including viruses, bacteria and fungi. To this end, T cells undergo a very strict educational program in the thymus, during which both non-functional and self-reactive T cell clones are eliminated by means of positive and negative selection1.Thymic epithelial cells (TECs) have an indispensable role in these processes, and previous studies have shown the notable heterogeneity of these cells2–7. Here, using multiomic analysis, we provide further insights into the functional and developmental diversity of TECs in mice, and reveal a detailed atlas of the TEC compartment according to cell transcriptional states and chromatin landscapes. Our analysis highlights unconventional TEC subsets that are similar to functionally well-defined parenchymal populations, including endocrine cells, microfold cells and myocytes. By focusing on the endocrine and microfold TEC populations, we show that endocrine TECs require Insm1 for their development and are crucial to maintaining thymus cellularity in a ghrelin-dependent manner; by contrast, microfold TECs require Spib for their development and are essential for the generation of thymic IgA+ plasma cells. Collectively, our study reveals that medullary TECs have the potential to differentiate into various types of molecularly distinct and functionally defined cells, which not only contribute to the induction of central tolerance, but also regulate the homeostasis of other thymus-resident populations. Multiomic analyses of mouse thymic epithelial cells identify several unconventional subsets that are mimetics of various populations of terminally differentiated parenchymal cells and provide insights into their development, molecular features and function.
DOI: 10.1038/s41586-023-06512-8
Source: https://www.nature.com/articles/s41586-023-06512-8
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
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
