LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Neutrophil developmental defects cause hyperinflammation in cherubism

Photo by claybanks from unsplash

Cherubism is a rare autosomal dominant disease caused mainly by a P416R point mutation of Src homology 3 Domain Binding Protein 2 (SH3BP2). Though macrophages and osteoblasts were thought to… Click to show full abstract

Cherubism is a rare autosomal dominant disease caused mainly by a P416R point mutation of Src homology 3 Domain Binding Protein 2 (SH3BP2). Though macrophages and osteoblasts were thought to be the major contributors to the pathology in the past, the involvement of neutrophils in cherubism has been demonstrated by the increasing neutrophil infiltration and extensive neutrophil extracellular trap formation in the lesion recently. Here, we observed decreased expression of lineage marker Ly6G and impaired integrin activation on neutrophils, indicating a developmental defect of neutrophils in cherubism mice carrying the SH3BP2 P416R mutation. Furthermore, we performed single-cell RNA sequencing and compared transcriptomes between blood neutrophils, bone marrow neutrophils, and bone marrow leukocyte progenitors from wildtype and SH3BP2 P416R mice. RNA velocity and pathway analysis show that mutated neutrophils have stalled in the early stage of neutrophil development and failed to mature into granzyme pathway-enhanced, NET-formation-restrained mature neutrophil population in wildtype. Together, our study first illustrates the neutrophil development defects in cherubism as a mechanism for hyperinflammation characterized in cherubism. Ziming Cao and Keaton Karlinsey contributed equally. Beiyan Zhou, I-Ping Chen and Zhichao Fan are co-corresponding authors. This research was supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute, USA (R01HL145454), and a startup fund from UConn Health. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Keywords: hyperinflammation; defects cause; neutrophil developmental; physiology; developmental defects; cherubism

Journal Title: Physiology
Year Published: 2023

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.