Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation
Year: 2020
Type: article
Abstract: Murine mast cells (MCs) contain two lineages: inducible bone marrow-derived mucosal MCs (MMCs) and constitutive embryonic-derived connective tissue MCs (CTMCs). Here, we use RNA sequencing, flow cytometry, and genetic deletion in two allergic lung inflammation models to define these two lineages. We found that inducible MCs, marked by β7 integrin expression, are highly distinct from airway CTMCs at rest and during inflammation and unaffected by targeted CTMC deletion. β7High MCs expand and mature during lung inflammation as part of a TGF-β-inducible transcriptional program that includes the MMC-associated proteases Mcpt1 and Mcpt2, the basophil-associated protease Mcpt8, granule components, and the epithelial-binding αE integrin. In vitro studies using bone marrow-derived MCs (BMMCs) identified a requirement for SCF in this this TGF-β-mediated development and found that epithelial cells directly elicit TGF-β-dependent BMMC up-regulation of mMCP-1 and αE integrin. Thus, our findings characterize the expansion of a distinct inducible MC subset in C57BL/6 mice and highlight the potential for epithelium to direct MMC development.
DOI: 10.1084/jem.20200321
Institutions: Brigham and Women's Hospital, Harvard University
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: hybrid
Awards: Oxysterol Regulation of Mast Cell Biology, CysLT and P2Y Receptors in Lung Inflammation, Allergic Pulmonary Inflammation Through the Dectin-2 Pathway, G7295586222, Optimizing EP receptor subtype targeting for asthma therapy, Eicosanoid Networks in Aspirin Hypersensitivity, Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease, Airway Inflammation and Airway Remodeling in Severe Asthma, Type 2 Inflammation and Remodeling Elicited Through an LTE4/OXGR1-dependent pathway, Immunologic Basis of Resistance and Hypersensitivity
OpenAlex ID: W3087080470