Interpretable inflammation landscape of circulating immune cells

Inflammation is a biological phenomenon beneficial for homeostasis, but it is unfavorable if dysregulated. Although major progress has been made in characterizing inflammation in specific diseases, a global, holistic understanding is still elusive. This is particularly intriguing, considering its function for human health and the potential for modern medicine if fully deciphered. In this study, we leveraged advances in single-cell transcriptomics to delineate inflammatory processes of circulating immune cells during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of more than 6.5 million peripheral blood mononuclear cells from 1,047 patients (56% female, 43% male) and 19 diseases allowed us to learn a comprehensive model of inflammation in circulating immune cells. The atlas expands current knowledge of the biology of inflammation of immune-mediated diseases, acute and chronic inflammatory diseases, infections and solid tumors and lays the foundation to develop a disease classification framework using unsupervised as well as explainable machine learning. Beyond a disease-centered analysis, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting discriminative inflammation-related genes to further understand mechanisms of inflammation. We present a rich resource for the community and lay the groundwork for learning a classifier for inflammatory diseases, presenting cells in circulation as living biomarkers.

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Publication Details

Journal
Nature Medicine
Published
2026-01-12
DOI
https://doi.org/10.1038/s41591-025-04126-3
Citations
1
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
22.24
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article

Interpretable inflammation landscape of circulating immune cells

Violeta Serra, Britta Siegmund, Tessa Kole, Silvia M. Vidal et al.
1 citations
Nature Medicine
Single-cell and spatial transcriptomics
22.24
article

Interpretable inflammation landscape of circulating immune cells

Violeta Serra, Britta Siegmund, Tessa Kole, Silvia M. Vidal, Juan C. Nieto, Martin Banchero, Davide Maspero, José Liñares-Blanco, Francesco Craighero, M Nawijn, Rachelly Normand, Eugeni Domènech, G. Girolomoni, Maria Boulougouri, Ernest Choy, Sergio Aguilar-Fernández, Laura Jiménez-Gracia, Ángela Sanzo-Machuca, Miren Berasategi, Hoang Anh Tran, Juan D. Cañete, J.D. Tornero, M. Van den Berge, Holger Heyn, Sara Marsal, JM Carrascosa, Azucena Salas, Gin Caratù, Sabine Tejpar, Max Ruiz, Antonio Fernández. Nebro, Hoang A. Tran, Petra van der Velde, Ricardo O. Ramirez Flores, Adrià Aterido, Javier P. Gisbert, Alexandra-Chloé Villani, Domenica Marchese, Yourae Hong, Antonio Julià, Julio Saez-Rodriguez, Eva Román, Jacquelyn Nestor
article en
1 citations

Abstract

Inflammation is a biological phenomenon beneficial for homeostasis, but it is unfavorable if dysregulated. Although major progress has been made in characterizing inflammation in specific diseases, a global, holistic understanding is still elusive. This is particularly intriguing, considering its function for human health and the potential for modern medicine if fully deciphered. In this study, we leveraged advances in single-cell transcriptomics to delineate inflammatory processes of circulating immune cells during infection, immune-mediated inflammatory diseases and cancer. Our single-cell atlas of more than 6.5 million peripheral blood mononuclear cells from 1,047 patients (56% female, 43% male) and 19 diseases allowed us to learn a comprehensive model of inflammation in circulating immune cells. The atlas expands current knowledge of the biology of inflammation of immune-mediated diseases, acute and chronic inflammatory diseases, infections and solid tumors and lays the foundation to develop a disease classification framework using unsupervised as well as explainable machine learning. Beyond a disease-centered analysis, we charted altered activity of inflammatory molecules in peripheral blood cells, depicting discriminative inflammation-related genes to further understand mechanisms of inflammation. We present a rich resource for the community and lay the groundwork for learning a classifier for inflammatory diseases, presenting cells in circulation as living biomarkers.

Nature MedicineVol. 32(2)
Broad Institute (US), Universitat de Vic - Universitat Central de Catalunya (ES), University of Verona (IT), European Bioinformatics Institute (GB), University Medical Center Groningen (NL), Harvard University (US), Rafael Advanced Defense Systems (Israel) (IL), University of Groningen (NL), Universidad de Granada (ES), Heidelberg University (DE), Instituto de Salud Carlos III (ES), Hospital de Sant Pau (ES), University Hospital Heidelberg (DE), Humboldt-Universität zu Berlin (DE), Massachusetts General Hospital (US), Hospital Universitario de Guadalajara (ES), Centro de Investigación en Red en Enfermedades Cardiovasculares (ES), Vall d'Hebron Institut de Recerca (ES), Sociedad Española de Trombosis y Hemostasia (ES), Hospital Regional Universitario de Málaga (ES), Hospital Universitario de La Princesa (ES), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (ES), Centro Nacional de Análisis Genómico (ES), Hospital Universitari Germans Trias i Pujol (ES), Fundació Clínic per a la Recerca Biomèdica (ES), Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (ES), Instituto de Investigación Biomédica de Málaga (ES), Vall d'Hebron Institute of Oncology (ES), École Polytechnique Fédérale de Lausanne (CH), Universidad Autónoma de Madrid (ES), Universitat de Barcelona (ES), Charité - Universitätsmedizin Berlin (DE), Cardiff University (GB), Universidad de Málaga (ES), KU Leuven (BE)
Reduced inequalities
Openalex Percentile: Top 3%
Single-cell and spatial transcriptomics
22.24
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