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

• DOI: 10.1016/j.celrep.2021.108974
• Publication Date: 2021-04-15T14:23:11Z
• Authors: Matthew J. Camiolo; Xiaoying Zhou; Timothy B. Oriss; Qi Yan; Michael Gorry; William Horne; John B. Trudeau; Kathryn Scholl; Wei Chen; Jay K. Kolls; Prabir Ray; Florian J. Weisel; Nadine M. Weisel; Nima Aghaeepour; Kari Nadeau; Sally E. Wenzel; Anuradha Ray
• Keywords: severe asthma; CD4-Positive T-Lymphocytes; Proteomics; 0301 basic medicine; QH301-705.5; Adaptive Immunity; CD8-Positive T-Lymphocytes; Article; Machine Learning; Interferon-gamma; 03 medical and health sciences; Adrenal Cortex Hormones; Humans; Anti-Asthmatic Agents; Biology (General); BAL; Receptors, IgE; Gene Expression Profiling; Interleukin-7; Macrophages; multi-omics; Asthma; Immunity, Innate; Interleukin-10; 3. Good health; Gene Expression Regulation; Case-Control Studies; CyTOF; immune; RNA-seq; Bronchoalveolar Lavage Fluid; Immunologic Memory

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.