Open AccessLineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation
Author(s) -
Tahereh Derakhshan,
Sachin K. Samuchiwal,
Nils Hallen,
Lora G. Bankova,
Joshua A. Boyce,
Nora A. Barrett,
K. Frank Austen,
Daniel F. Dwyer
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200321
Subject(s) - biology , inflammation , allergic inflammation , stromal cell , immunology , thymic stromal lymphopoietin , bone marrow , microbiology and biotechnology , proteases , respiratory epithelium , flow cytometry , haematopoiesis , epithelium , cancer research , genetics , stem cell , biochemistry , enzyme
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 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.