scRNA-seq profiling of human granulocytes reveals expansion of developmentally flexible neutrophil precursors with mixed neutrophil and eosinophil properties in asthma

Author:

Haruna Nana-Fatima1,Politanska Yuliya2,Connelly Andrew R1,O’Connor Kathrine3,Bhattacharya Sourav3,Miklaszewski Grace E1,Pérez-Leonor Xóchitl G2,Rerko Geddy2,Hentenaar Ian T4,Nguyen Doan C4,Molina Pedro Alberto Lamothe4,Bochner Bruce S1ORCID,Abdala-Valencia Hiam2,Gill Michelle A3,Lee F Eun-Hyung4,Berdnikovs Sergejs1ORCID

Affiliation:

1. Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine , 240 East Huron, McGaw M-316, Chicago, IL 60611 , United States

2. Division of Pulmonary and Critical Care, Northwestern University Feinberg School of Medicine , 303 East Superior, Simpson Querrey Biomedical Research Center 5-407, Chicago, IL 60611 , United States

3. Division of Allergy and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine in St. Louis , 1 Childrens Place, St. Louis, MO 63110 , United States

4. Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University , 615 Michael Street, Suite 205, Atlanta, GA 30322 , United States

Abstract

Abstract Neutrophils and eosinophils share common hematopoietic precursors and usually diverge into distinct lineages with unique markers before being released from their hematopoietic site, which is the bone marrow (BM). However, previous studies identified an immature Ly6g(+) Il-5Rα(+) neutrophil population in mouse BM, expressing both neutrophil and eosinophil markers suggesting hematopoietic flexibility. Moreover, others have reported neutrophil populations expressing eosinophil-specific cell surface markers in tissues and altered disease states, confusing the field regarding eosinophil origins, function, and classification. Despite these reports, it is still unclear whether hematopoietic flexibility exists in human granulocytes. To answer this, we utilized single-cell RNA sequencing and cellular indexing of transcriptomes and epitopes by sequencing to profile human BM and circulating neutrophils and eosinophils at different stages of differentiation and determine whether neutrophil plasticity plays role in asthmatic inflammation. We show that immature metamyelocyte neutrophils in humans expand during severe asthmatic inflammation and express both neutrophil and eosinophil markers. We also show an increase in trilobed eosinophils with mixed neutrophil and eosinophil markers in allergic asthma and that interleukin-5 promotes differentiation of immature blood neutrophils into trilobed eosinophilic phenotypes, suggesting a mechanism of emergency granulopoiesis to promote myeloid inflammatory or remodeling response in patients with chronic asthma. By providing insights into unexpectedly flexible granulocyte biology and demonstrating emergency hematopoiesis in asthma, our results highlight the importance of granulocyte plasticity in eosinophil development and allergic diseases.

Funder

Ernest Bazley Foundation

Publisher

Oxford University Press (OUP)

Reference48 articles.

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