GM-CSF derived from alveolar type 2 cells promotes CD301b+ cDC2 generation and allergic airway inflammation.

IF 16.3 1区医学 Q1 IMMUNOLOGY

Science Immunology Pub Date : 2025-08-08 DOI:10.1126/sciimmunol.adt0688

Julia Gschwend,Antonie Lechner,Nikolaos D Sidiropoulos,Paul Maier,Tilde Andersson,Flurin Sturzenegger,Basak Corak,Nina Brander,David A Bejarano,Elina Wells,Sandra P Melo,Joana R D Martins,Maximilian Nitschké,Ari B Molofsky,Andreas Schlitzer,Isabelle C Arnold,Sarah Mundt,Burkhard Becher,Manfred Kopf,Hubert Rehrauer,Christoph Schneider

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引用次数: 0

Abstract

Pulmonary conventional dendritic cells (cDCs) are functionally and phenotypically heterogeneous antigen-presenting cells essential for orchestrating adaptive immune responses in the lung. Here, we define a cell-intrinsic role for granulocyte-macrophage colony-stimulating factor (GM-CSF) signaling in the development of a CD301b+ subset of terminally differentiated cDC2s, in addition to CD103+XCR1+ cDC1s. Unbiased single-cell transcriptomic profiling of CD11c+ cells identified both immature and differentiated lung cDC populations. GM-CSF deficiency disrupted antiapoptotic Bcl2a1 up-regulation and impaired progression to the CD301b+ transcriptional state. Despite the positioning of CD301b+ cDC2s in lymphoid cell-rich adventitial cuff areas, hematopoietic GM-CSF was dispensable for their development. Instead, alveolar epithelial type 2 cell-derived GM-CSF was required for CD301b+ cDC2 formation and pulmonary type 2 immune responses, highlighting the central role of GM-CSF signaling in shaping the pulmonary myeloid landscape.

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来源于肺泡2型细胞的GM-CSF促进CD301b+ cDC2的生成和过敏性气道炎症。

肺常规树突状细胞（cDCs）是功能和表型上异质性的抗原呈递细胞，对协调肺适应性免疫反应至关重要。在这里，我们定义了粒细胞-巨噬细胞集落刺激因子（GM-CSF）信号在CD301b+终分化cDC2s亚群发展中的细胞内在作用，以及CD103+XCR1+ cDC1s。CD11c+细胞的无偏见单细胞转录组学分析鉴定了未成熟和分化的肺cDC群体。GM-CSF缺乏破坏抗凋亡的Bcl2a1上调和CD301b+转录状态的进展。尽管CD301b+ cDC2s位于富含淋巴样细胞的外袖区，但造血GM-CSF对于它们的发育是不可或缺的。相反，肺泡上皮2型细胞来源的GM-CSF是CD301b+ cDC2形成和肺2型免疫应答所必需的，这突出了GM-CSF信号在形成肺髓细胞景观中的核心作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Science Immunology Immunology and Microbiology-Immunology

CiteScore

32.90

自引率

2.00%

发文量

183

期刊介绍： Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.