High-dimensional profiling clusters asthma severity by lymphoid and non-lymphoid status.

Journal: Cell reports
PMID: 33852838

Abstract

Clinical definitions of asthma fail to capture the heterogeneity of immune dysfunction in severe, treatment-refractory disease. Applying mass cytometry and machine learning to bronchoalveolar lavage (BAL) cells, we find that corticosteroid-resistant asthma patients cluster largely into two groups: one enriched in interleukin (IL)-4 innate immune cells and another dominated by interferon (IFN)-γ T cells, including tissue-resident memory cells. In contrast, BAL cells of a healthier population are enriched in IL-10 macrophages. To better understand cellular mediators of severe asthma, we developed the Immune Cell Linkage through Exploratory Matrices (ICLite) algorithm to perform deconvolution of bulk RNA sequencing of mixed-cell populations. Signatures of mitosis and IL-7 signaling in CD206FcεRICD127IL-4 innate cells in one patient group, contrasting with adaptive immune response in T cells in the other, are preserved across technologies. Transcriptional signatures uncovered by ICLite identify T-cell-high and T-cell-poor severe asthma patients in an independent cohort, suggesting broad applicability of our findings.

Authors

  • Matthew J Camiolo
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Center for Systems Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
  • Xiaoying Zhou
    School of Information Resource Management, Renmin University of China, Beijing, China.
  • Timothy B Oriss
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Qi Yan
  • Michael Gorry
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • William Horne
    Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • John B Trudeau
    Department of Environmental Medicine and Occupational Health, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Kathryn Scholl
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Wei Chen
    Department of Urology, Zigong Fourth People's Hospital, Sichuan, China.
  • Jay K Kolls
    Department of Medicine and Center for Translational Research in Infection and Inflammation Tulane School of Medicine, New Orleans, LA, USA.
  • Prabir Ray
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Florian J Weisel
    Departments of Anesthesiology, Pain, and Peri-operative Medicine and Biomedical Data Sciences, Stanford University, Stanford, CA, USA.
  • Nadine M Weisel
    Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Nima Aghaeepour
    Departments of Anesthesiology, Pain, and Peri-operative Medicine and Biomedical Data Sciences, Stanford University, Stanford, CA, USA.
  • Kari Nadeau
    Department of Environmental Health, T. H. Chan School of Public Health, Harvard University, Boston, Mass.
  • Sally E Wenzel
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Environmental Medicine and Occupational Health, Graduate School of Public Health, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
  • Anuradha Ray
    Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. Electronic address: raya@pitt.edu.

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