Single-cell clonal tracing of glandular and circulating T cells identifies a population of CD9+CD8+T cells in primary Sjogren's syndrome

Single-cell clonal tracing of glandular and circulating T cells identifies a population of CD9+CD8+T cells in primary Sjogren's syndrome
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DOI:
10.1093/jleuko/qiad071
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发表时间:
2024-04-29
影响因子:
5.5
通讯作者:
Wu,Yuzhang
Wu,Yuzhang
中科院分区:
医学3区
文献类型:
--
作者:
Chang,Ling;Zheng,Zihan;Wu,Yuzhang

文献摘要

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原发性干燥综合征(PSS)是一种复杂的慢性自身免疫性疾病,其外分泌腺的局部组织损害与全身包括皮肤在内的组织的更广泛的全身受累相结合。这些综合表现会对患者的健康和生活质量产生负面影响。虽然先前的研究报道了PSS患者外周血中免疫细胞组成与健康对照组存在差异,但这些患者受损外分泌腺的详细免疫细胞图谱仍然缺乏。通过对配对的外周血样和唾液腺活检中的免疫细胞进行单细胞转录和序列测定,我们初步描绘了PSS中适应性免疫反应的图景。我们描述了迄今为止一直被低估的循环和腺体免疫反应之间的一些分歧点,并确定了一种新的CD8+CD9+细胞群体,具有组织驻留特性,在PSS患者的唾液腺中高度丰富。通过与其他测序数据的比较分析,我们还观察到这些细胞与皮肤血管炎病变中发现的组织驻留记忆细胞之间的潜在联系。综上所述,这些结果表明CD8+CD9+细胞在介导与PSS和其他自身免疫性疾病相关的腺体和全身效应中具有潜在的作用。
Primary Sjogren's syndrome (pSS) is a complex chronic autoimmune disease in which local tissue damage in exocrine glands is combined with broader systemic involvement across the body in tissues including the skin. These combined manifestations negatively impact patient health and quality of life. While studies have previously reported differences in immune cell composition in the peripheral blood of pSS patients relative to healthy control subjects, a detailed immune cell landscape of the damaged exocrine glands of these patients remains lacking. Through single-cell transcriptomics and repertoire sequencing of immune cells in paired peripheral blood samples and salivary gland biopsies, we present here a preliminary picture of adaptive immune response in pSS. We characterize a number of points of divergence between circulating and glandular immune responses that have been hitherto underappreciated, and identify a novel population of CD8+ CD9+ cells with tissue-residential properties that are highly enriched in the salivary glands of pSS patients. Through comparative analyses with other sequencing data, we also observe a potential connection between these cells and the tissue-resident memory cells found in cutaneous vasculitis lesions. Together, these results indicate a potential role for CD8+ CD9+ cells in mediating glandular and systemic effects associated with pSS and other autoimmune disorders.