Single-cell RNA-sequencing of circulating eosinophils from asthma patients reveals an inflammatory signature
Kyndal Goss,
Melanie L. Grant,
Cherish Caldwell,
Gail A. Dallalio,
Susan T. Stephenson,
Anne M. Fitzpatrick,
Edwin M. Horwitz
Affiliations
Kyndal Goss
Marcus Center for Advanced Cellular Therapy, Atlanta, GA, USA; Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Hematology/Oncology, Atlanta, GA, USA
Melanie L. Grant
Marcus Center for Advanced Cellular Therapy, Atlanta, GA, USA; Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Hematology/Oncology, Atlanta, GA, USA
Cherish Caldwell
Division of Pulmonary Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA
Gail A. Dallalio
Division of Pulmonary Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Pulmonary Medicine, Atlanta, GA, USA
Susan T. Stephenson
Division of Pulmonary Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Pulmonary Medicine, Atlanta, GA, USA
Anne M. Fitzpatrick
Division of Pulmonary Medicine, Children’s Healthcare of Atlanta, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Pulmonary Medicine, Atlanta, GA, USA; Corresponding author
Edwin M. Horwitz
Marcus Center for Advanced Cellular Therapy, Atlanta, GA, USA; Aflac Cancer & Blood Disorders Center, Atlanta, GA, USA; Emory University Department of Pediatrics, Division of Hematology/Oncology, Atlanta, GA, USA; Corresponding author
Summary: Asthma is the most common chronic lung disorder in the United States. While asthma is heterogeneous, blood eosinophils are central to the pathogenesis in most cases. Yet, the power of modern omics has not been widely applied to the study of asthma eosinophils. We report single cell RNA sequencing of blood eosinophils obtained from patients with severe asthma, mild asthma, and healthy volunteers. The eosinophils from asthma patients showed marked heterogeneity in the population and, as with healthy controls, clustered into 3 subsets suggesting at least 3 gene expression states circulating in the blood. Eosinophils from asthma patients had an inflammatory gene signature with enrichment of interferon α and γ pathways. Moreover, a greater fraction of these eosinophils expressed CCR3, the chemokine receptor that mediates trafficking to inflamed tissues and activates eosinophils. Our data support implementation of larger studies to define the transcriptional drivers of asthma.