小柯机器人

奥地利科学院分子医学研究中心Georg Stary和Christoph Bock共同合作，近期取得重要工作进展。他们通过研究单细胞和空间转录组学揭示出驱动肉芽肿形成的异常淋巴样发育程序。相关研究成果2023年2月6日在线发表于《免疫》杂志上。

据介绍，肉芽肿是免疫细胞的团块，可以在各种器官中形成。大多数肉芽肿看似无结构，但它们与淋巴器官有些相似之处。

为了更好地理解肉芽肿的形成，研究人员对结节病患者的肉芽肿进行了单细胞测序和空间转录组学分析，并从生物信息学角度重建了潜在的基因调控网络。研究人员在肉芽肿中发现了一种免疫刺激环境，它重新调整了与淋巴器官发育相关的转录程序。肉芽肿的形成遵循特征性的空间模式，涉及与免疫代谢、细胞因子和趋化因子信号传导以及细胞外基质重塑相关的基因。三种细胞类型成为肉芽肿形成的关键因素：代谢重编程的巨噬细胞、产生细胞因子的Th17.1细胞和具有炎症和组织重塑表型的成纤维细胞。在结节病小鼠模型中，对其中一种已鉴定过程的药理学抑制减弱了肉芽肿的形成。

总之，研究人员表明，人类肉芽肿在异常组合中采用了正常淋巴器官发育的特征，表明肉芽肿构成了异常的淋巴器官。

附：英文原文

Title: Single-cell and spatial transcriptomics reveal aberrant lymphoid developmental programs driving granuloma formation

Author: Thomas Krausgruber, Anna Redl, Daniele Barreca, Konstantin Doberer, Daria Romanovskaia, Lina Dobnikar, Maria Guarini, Luisa Unterluggauer, Lisa Kleissl, Denise Atzmüller, Carolina Mayerhofer, Aglaja Kopf, Simona Saluzzo, Clarice X. Lim, Praveen Rexie, Thomas Weichhart, Christoph Bock, Georg Stary

Issue&Volume: 2023-02-06

Abstract: Granulomas are lumps of immune cells that can form in various organs. Most granulomas appear unstructured, yet they have some resemblance to lymphoid organs. To better understand granuloma formation, we performed single-cell sequencing and spatial transcriptomics on granulomas from patients with sarcoidosis and bioinformatically reconstructed the underlying gene regulatory networks. We discovered an immune stimulatory environment in granulomas that repurposes transcriptional programs associated with lymphoid organ development. Granuloma formation followed characteristic spatial patterns and involved genes linked to immunometabolism, cytokine and chemokine signaling, and extracellular matrix remodeling. Three cell types emerged as key players in granuloma formation: metabolically reprogrammed macrophages, cytokine-producing Th17.1 cells, and fibroblasts with inflammatory and tissue-remodeling phenotypes. Pharmacological inhibition of one of the identified processes attenuated granuloma formation in a sarcoidosis mouse model. We show that human granulomas adopt characteristic aspects of normal lymphoid organ development in aberrant combinations, indicating that granulomas constitute aberrant lymphoid organs.

DOI: 10.1016/j.immuni.2023.01.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00024-9

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