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

MJ Camiolo, X Zhou, TB Oriss, Q Yan, M Gorry… - Cell reports, 2021 - cell.com
MJ Camiolo, X Zhou, TB Oriss, Q Yan, M Gorry, W Horne, JB Trudeau, K Scholl, W Chen
Cell reports, 2021cell.com
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 …
Summary
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 CD206FcεRI+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.
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