Tissue-resident immune cells drive genetic risk in autoimmune and lung diseases
Common genetic variants are associated with risk of lung and autoimmune diseases. However, we have a limited understanding of the pathological effects of these disease variants, specifically in tissue-resident immune cells at the frontier of infection and disease in the lung. To address this, we performed single-cell expression quantitative trait locus (eQTL) analysis across 29 distinct immune cell subsets isolated from lung tissue. Colocalization analysis of lung immune cell eQTLs with genome-wide association study (GWAS) signals from lung diseases, and infectious and autoimmune diseases, implicate disease-associated variants and their target genes functioning in a single or restricted group of cell types. Several genes, including ZFP57, showed significant colocalization between lung immune cell eQTLs and GWAS signals from multiple systemic and organ-restricted autoimmune diseases, highlighting shared genetic mechanisms underlying the risk of disease. Overall, our study shows that disease-associated variants from a wide range of autoimmune diseases impact gene expression in tissue-resident immune cell types ( https://lung.dice-database.org ).
Authors
- Brendan Ha
- Vicente Fajardo (ORCID: https://orcid.org/0000-0002-1578-7438)
- Pandurangan Vijayanand (ORCID: https://orcid.org/0000-0001-7067-9723)
- Aiman Alzetani (ORCID: https://orcid.org/0000-0002-3373-6714)
- Mitchell Kronenberg (ORCID: https://orcid.org/0000-0001-6318-6445)
- Bjoern Peters (ORCID: https://orcid.org/0000-0002-8457-6693)
- H Simon
- Lindsey Chudley
- Anusha-Preethi Ganesan (ORCID: https://orcid.org/0000-0003-3775-9996)
- Michael Shackcloth (ORCID: https://orcid.org/0000-0002-6494-9907)
- Jason Greenbaum (ORCID: https://orcid.org/0000-0002-1381-0390)
- Benjamin Joachim Schmiedel (ORCID: https://orcid.org/0000-0002-9103-9378)
- Christian H. Ottensmeier (ORCID: https://orcid.org/0000-0003-3619-1657)
- Cristian González-Colín (ORCID: https://orcid.org/0000-0002-3920-3740)
- Ignacio E. Ramírez‐Bernabé (ORCID: https://orcid.org/0009-0004-5026-9128)
- J. Hernández (ORCID: https://orcid.org/0000-0002-1292-2307)
- Elizabeth Márquez-Gómez (ORCID: https://orcid.org/0009-0009-5669-9432)
- Edwin Woo
- Judith Cave
- Serena J. Chee
- Angel De la Cruz Castillo
- Vivek Chandra
- April Cano (ORCID: https://orcid.org/0009-0006-4324-0727)
- Johannes Ottensmeier (ORCID: https://orcid.org/0009-0003-7081-7964)
Institutions
- La Jolla Institute for Immunology (US)
- University of Liverpool (GB)
- University Hospital Southampton NHS Foundation Trust (GB)
- Clatterbridge Cancer Centre NHS Foundation Trust (GB)
- University of California San Diego (US)
- Liverpool Heart and Chest Hospital (GB)
- Rady Children's Hospital-San Diego (US)
- La Jolla Alcohol Research (US)
- National Institute of Genomic Medicine (MX)
- NIHR Southampton Biomedical Research Centre (GB)
- Universidad Nacional Autónoma de México (MX)
Publication Details
- Journal
- Nature Immunology
- Published
- 2026-08-03
- DOI
- https://doi.org/10.1038/s41590-026-02596-2
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Institutes of Health