Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation

Guanrui Liao¹, Tsuguhisa Nakayama², Bokai Zhu³, Ivan T Lee², Jason Yeung¹, Yao Yu Yeo¹, Yuzhou Chang⁴, Cankun Wang⁵, Steven Chun-Kang Liao⁶, Dingani Nkosi⁷, Axel Renteria², Dawn T Bravo², Jonathan B Overdevest⁸, Carol H Yan⁹, David Zarabanda², Philip A Gall², Sachi S Dholakia², Nicole A Borchard², Angela Yang², Dayoung Kim², Zara M Patel², Peter H Hwang², Dhananjay Wagh¹⁰, John Coller¹⁰, Katie M Phillips¹¹, Michael T Chang², Matt Lechner¹², Zihai Li¹³, Te-Huei Yeh¹⁴, Garry Nolan³, Maria Serena Longhi¹⁵, Vassiliki Boussiotis¹⁶, Dan H Barouch¹, Qin Ma⁵, Jayakar V Nayak¹⁷, Sizun Jiang¹⁸

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
² Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁴ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁵ Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁶ Department of Otolaryngology, National Taiwan University Hospital, Yunlin Branch, Yunlin County, Douliu 640203, Taiwan.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁸ Department of Otolaryngology-Head and Neck Surgery, Columbia University School of Medicine, New York, NY 10032, USA.
⁹ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁰ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹¹ Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati School of Medicine, Cincinnati, OH 45221, USA.
¹² UCL Head and Neck Academic Center, Division of Surgery and Interventional Science, University College London, London WC1E 6BT, UK.
¹³ Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
¹⁴ Department of Otolaryngology, National Taiwan University Hospital Hsin-Chu Branch, Biomedical Park Hospital, Hsinchu 302058, Taiwan.
¹⁵ Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁶ Department of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Otolaryngology-Head and Neck Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. Electronic address: jnayak@stanford.edu.
¹⁸ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Dana Farber Cancer Institute, Boston, MA 02115, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: sjiang3@bidmc.harvard.edu.

PMID: 40945518
DOI: 10.1016/j.immuni.2025.08.009

Free article

Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation

Guanrui Liao et al. Immunity. 2025.

Free article

. 2025 Oct 14;58(10):2593-2608.e6.

doi: 10.1016/j.immuni.2025.08.009. Epub 2025 Sep 12.

Authors

Affiliations

¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
² Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA.
³ Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA.
⁴ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁵ Department of Biomedical Informatics, The Ohio State University, Columbus, OH 43210, USA; Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
⁶ Department of Otolaryngology, National Taiwan University Hospital, Yunlin Branch, Yunlin County, Douliu 640203, Taiwan.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
⁸ Department of Otolaryngology-Head and Neck Surgery, Columbia University School of Medicine, New York, NY 10032, USA.
⁹ Division of Otolaryngology-Head and Neck Surgery, Department of Surgery, University of California, San Diego School of Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
¹⁰ Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
¹¹ Department of Otolaryngology-Head and Neck Surgery, University of Cincinnati School of Medicine, Cincinnati, OH 45221, USA.
¹² UCL Head and Neck Academic Center, Division of Surgery and Interventional Science, University College London, London WC1E 6BT, UK.
¹³ Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
¹⁴ Department of Otolaryngology, National Taiwan University Hospital Hsin-Chu Branch, Biomedical Park Hospital, Hsinchu 302058, Taiwan.
¹⁵ Department of Anesthesia, Critical Care & Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁶ Department of Hematology-Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
¹⁷ Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Otolaryngology-Head and Neck Surgery, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. Electronic address: jnayak@stanford.edu.
¹⁸ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Dana Farber Cancer Institute, Boston, MA 02115, USA; The Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic address: sjiang3@bidmc.harvard.edu.

PMID: 40945518
DOI: 10.1016/j.immuni.2025.08.009

Abstract

Chronic rhinosinusitis (CRS) is a common chronic inflammatory disease of the sinonasal cavity affecting millions worldwide. Its complex pathophysiology remains poorly understood, with emerging evidence implicating interactions between diverse immune and epithelial cells in disease progression. We applied single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics to both dissociated and intact human tissues from individuals with CRS with and without nasal polyps and compared them with controls. We revealed mechanisms of macrophage-eosinophil recruitment, CD4⁺ and CD8⁺ T cell dysregulation, and mast cell enrichment. We identified key immune-epithelial interactions in tissue remodeling, particularly involving basal progenitor and tuft cells. A distinct basal cell trajectory was implicated in nasal polyp formation. Orthogonal validation with spatial transcriptomics from >100 individuals with CRS revealed conserved tissue remodeling features. Our study provides insights into CRS pathophysiology, highlighting immune-epithelial interactions as potential therapeutic targets in chronic inflammation, also serving as a resource for dissecting immune disease mechanisms.

Keywords: autoimmunity; chronic rhinosinusitis; inflammation; nasal epithelium; nasal polyp; remodeling; single-cell; spatial transcriptomics; type 2 inflammation.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests S.J. is a co-founder of Elucidate Bio Inc. and serves on its Board of Directors and Scientific Advisory Board and acknowledges research support from Sanofi and Roche unrelated to this work. G.N. is co-founder of IonPath Inc and Akoya Biosciences, Inc.; inventor on patent US9909167; and is a Scientific Advisory Board member for Akoya Biosciences, Inc. V.B. has patents on the programmed cell death 1 (PD-1) pathway licensed by Bristol-Myers Squibb, Roche, Merck, EMD Serono, Boehringer Ingelheim, AstraZeneca, Novartis, and Dako unrelated to this work. J.V.N. is a consultant with Sound Health, C2Dx, Aerin Medical, Acclarent/Integra, and SpirAir, all unrelated to this work.

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

LinkOut - more resources

Full Text Sources
- Elsevier Science
Medical
- MedlinePlus Health Information
Research Materials
- NCI CPTC Antibody Characterization Program

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation

Affiliations

Multi-scaled transcriptomics of chronically inflamed nasal epithelium reveals immune-epithelial dynamics and tissue remodeling in nasal polyp formation

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

LinkOut - more resources

Full Text Sources

Medical

Research Materials