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单细胞RNA测序荟萃分析揭示的基于趋化因子的细胞通讯的免疫疾病对话

Immune disease dialogue of chemokine-based cell communications as revealed by single-cell RNA sequencing meta-analysis.

作者信息

Rahman Mouly F, Kurlovs Andre H, Vodnala Munender, Meibalan Elamaran, Means Terry K, Nouri Nima, de Rinaldis Emanuele, Savova Virginia

机构信息

Precision Medicine and Computational Biology, Sanofi US, Cambridge, MA 02141, United States.

Immunology & Inflammation Research Therapeutic Area, Sanofi US, Cambridge, MA 02141, United States.

出版信息

bioRxiv. 2024 Jul 19:2024.07.17.603936. doi: 10.1101/2024.07.17.603936.

Abstract

Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge. To delineate disease-specific cell-cell communications involved in immune cell migration, we conducted a meta-analysis of publicly available single-cell RNA sequencing (scRNA-seq) data across diverse immune diseases and tissues. Our comprehensive analysis spanned multiple immune disorders affecting major organs: atopic dermatitis and psoriasis (skin), chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (lung), ulcerative colitis (colon), IgA nephropathy and lupus nephritis (kidney). By interrogating ligand-receptor (L-R) interactions, alterations in cell proportions, and differential gene expression, we unveiled intricate disease-specific and common immune cell chemoattraction and extravasation patterns. Our findings delineate disease-specific L-R networks and shed light on shared immune responses across tissues and diseases. Insights gleaned from this analysis hold promise for the development of targeted therapeutics aimed at modulating immune cell migration to mitigate inflammation and tissue damage. This nuanced understanding of immune cell dynamics at the single-cell resolution opens avenues for precision medicine in immune disease management.

摘要

免疫介导的疾病以异常免疫反应为特征,给全球健康带来了重大挑战。在炎症性疾病和自身免疫性疾病中,由组织驻留免疫细胞和非免疫细胞介导的免疫反应失调会引发慢性炎症和组织损伤,而外周免疫细胞向组织的渗出会加剧这种损伤。趋化因子受体在协调免疫细胞迁移中起关键作用,但解读跨细胞类型、疾病和组织的信号密码仍然是一个有待解决的挑战。为了描绘参与免疫细胞迁移的疾病特异性细胞间通讯,我们对多种免疫疾病和组织的公开单细胞RNA测序(scRNA-seq)数据进行了荟萃分析。我们的综合分析涵盖了影响主要器官的多种免疫疾病:特应性皮炎和银屑病(皮肤)、慢性阻塞性肺疾病和特发性肺纤维化(肺)、溃疡性结肠炎(结肠)、IgA肾病和狼疮性肾炎(肾脏)。通过研究配体-受体(L-R)相互作用、细胞比例变化和差异基因表达,我们揭示了复杂的疾病特异性和常见的免疫细胞趋化和渗出模式。我们的研究结果描绘了疾病特异性的L-R网络,并揭示了不同组织和疾病之间共享的免疫反应。从这项分析中获得的见解有望推动旨在调节免疫细胞迁移以减轻炎症和组织损伤的靶向治疗药物的开发。这种在单细胞分辨率下对免疫细胞动态的细致理解为免疫疾病管理中的精准医学开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4fbb/11275869/6f3dd315c8ce/nihpp-2024.07.17.603936v1-f0001.jpg

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