德国化学与生物化学研究所Sigmar Stricker课题组发现,表达转录因子Osr1的间充质细胞局部亚群协调淋巴结(LN)起始。这一研究成果于2023年5月8日发表在国际顶尖学术期刊《免疫》上。
通过谱系追踪,他们证明了表达Osr1的细胞子集是间充质淋巴组织组织者(LTo)祖细胞。通过研究Osr1+细胞的异质性,他们在不同解剖位置发现了不同的间充质LTo特征,鉴定了间充质LTo和LN相关脂肪组织的共同祖细胞。Osr1对于LN的起始、驱动独立于神经视黄酸的间充质LTo细胞的定型以及LN相关的淋巴血管组装至关重要。
LN的起始需要趋化因子CXCL13和CCL21的联合作用。他们的研究结果重新定义了间充质组织细胞的作用和身份,并通过提出LN起始中的合作细胞功能模型统一了目前的观点。
据悉,在发育过程中,LTo细胞在胚胎内的战略位置吸引淋巴组织诱导者(LTi)细胞,从而协调LN的形成。在LTi细胞的初始吸引过程中,LTo细胞的身份和功能仍然知之甚少。
附:英文原文
Title: A local subset of mesenchymal cells expressing the transcription factor Osr1 orchestrates lymph node initiation
Author: Pedro Vallecillo-García, Mickael Orgeur, Glenda Comai, Sophie Poehle-Kronnawitter, Cornelius Fischer, Marleen Gloger, Camille E. Dumas, Claudia Giesecke-Thiel, Sascha Sauer, Shahragim Tajbakhsh, Uta E. Hpken, Sigmar Stricker
Issue&Volume: 2023-05-08
Abstract: During development, lymph node (LN) initiation is coordinated by lymphoid tissue organizer(LTo) cells that attract lymphoid tissue inducer (LTi) cells at strategic positionswithin the embryo. The identity and function of LTo cells during the initial attractionof LTi cells remain poorly understood. Using lineage tracing, we demonstrated thata subset of Osr1-expressing cells was mesenchymal LTo progenitors. By investigating the heterogeneityof Osr1+ cells, we uncovered distinct mesenchymal LTo signatures at diverse anatomical locations,identifying a common progenitor of mesenchymal LTos and LN-associated adipose tissue.Osr1 was essential for LN initiation, driving the commitment of mesenchymal LTo cellsindependent of neural retinoic acid, and for LN-associated lymphatic vasculature assembly.The combined action of chemokines CXCL13 and CCL21 was required for LN initiation.Our results redefine the role and identity of mesenchymal organizer cells and unifycurrent views by proposing a model of cooperative cell function in LN initiation.
DOI: 10.1016/j.immuni.2023.04.014
Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00182-6
Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:43.474
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