Nayar Saba, Turner Jason D, Asam Saba, Fennell Eanna, Pugh Matthew, Colafrancesco Serena, Berardicurti Onorina, Smith Charlotte G, Flint Joe, Teodosio Ana, Iannizzotto Valentina, Gardner David H, van Roon Joel, Korsunsky Ilya, Howdle Dawn, Frei Andreas P, Lassen Kara G, Bowman Simon J, Ng Wan-Fai, Croft Adam P, Filer Andrew, Fisher Benjamin A, Buckley Christopher D, Barone Francesca
Rheumatology Research Group, Department of Inflammation and Ageing, College of Medicine & Health, University of Birmingham, Birmingham, UK.
National Institute for Health Research (NIHR) Birmingham Biomedical Research Centre, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Nat Commun. 2025 Jan 2;16(1):5. doi: 10.1038/s41467-024-54686-0.
Tertiary lymphoid structures play important roles in autoimmune and non-autoimmune conditions. While many of the molecular mechanisms involved in tertiary lymphoid structure formation have been identified, the cellular sources and temporal and spatial relationship remain unknown. Here we use combine single-cell RNA-sequencing, spatial transcriptomics and proteomics of minor salivary glands of patients with Sjogren's disease and Sicca Syndrome, with ex-vivo functional studies to construct a cellular and spatial map of key components involved in the formation and function of tertiary lymphoid structures. We confirm the presence of a fibroblast cell state and identify a pericyte/mural cell state with potential immunological functions. The identification of cellular properties associated with these structures and the molecular and functional interactions identified by this analysis may provide key therapeutic cues for tertiary lymphoid structures associated conditions in autoimmunity and cancer.
三级淋巴结构在自身免疫性和非自身免疫性疾病中发挥着重要作用。虽然已经确定了许多参与三级淋巴结构形成的分子机制，但细胞来源以及时间和空间关系仍然未知。在这里，我们结合干燥综合征和干燥综合征患者小唾液腺的单细胞RNA测序、空间转录组学和蛋白质组学，并进行体外功能研究，以构建参与三级淋巴结构形成和功能的关键成分的细胞和空间图谱。我们证实了一种成纤维细胞状态的存在，并鉴定出一种具有潜在免疫功能的周细胞/壁细胞状态。与这些结构相关的细胞特性的鉴定以及该分析确定的分子和功能相互作用可能为自身免疫和癌症中与三级淋巴结构相关的疾病提供关键的治疗线索。
