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

Cell Rep. 2021 Apr 13;35(2):108974. doi: 10.1016/j.celrep.2021.108974.


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 CD206-FcεRI+CD127+IL-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.

Keywords: BAL; CyTOF; FceRI+; ICLite; IFN-g; RNA-seq; clusters; immune; multi-omics; severe asthma.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Adrenal Cortex Hormones / therapeutic use
  • Anti-Asthmatic Agents / therapeutic use
  • Asthma / drug therapy
  • Asthma / genetics
  • Asthma / immunology*
  • Asthma / pathology
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / pathology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Case-Control Studies
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Immunity, Innate
  • Immunologic Memory
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Interleukin-7 / genetics
  • Interleukin-7 / immunology
  • Machine Learning*
  • Macrophages / immunology*
  • Macrophages / pathology
  • Proteomics / methods
  • Receptors, IgE / genetics
  • Receptors, IgE / immunology
  • Severity of Illness Index
  • Signal Transduction


  • Adrenal Cortex Hormones
  • Anti-Asthmatic Agents
  • FcepsilonRI alpha-chain, human
  • IFNG protein, human
  • IL10 protein, human
  • IL7 protein, human
  • Interleukin-7
  • Receptors, IgE
  • Interleukin-10
  • Interferon-gamma