Lineage-specific Regulation of Inducible and Constitutive Mast Cells in Allergic Airway Inflammation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2020 Sep 18

PMID 32946563

Citations 29

Authors

Tahereh Derakhshan

Sachin K Samuchiwal

Nils Hallen

Lora G Bankova

Joshua A Boyce

Nora A Barrett

K Frank Austen

Daniel F Dwyer

Affiliations

Soon will be listed here.

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.

Citing Articles

TGF-β1 Induces Mucosal Mast Cell Genes and is Negatively Regulated by the IL-3/ERK1/2 Axis.

Meurer S, Bronneberg G, Penners C, Kauffmann M, Braunschweig T, Liedtke C Cell Commun Signal. 2025; 23(1):76.

PMID: 39934802 PMC: 11817834. DOI: 10.1186/s12964-025-02048-8.

Human intraepithelial mast cell differentiation and effector function are directed by TGF-β signaling.

Derakhshan T, Hollers E, Perniss A, Ryan T, McGill A, Hacker J J Clin Invest. 2025; 135(1).

PMID: 39744949 PMC: 11684804. DOI: 10.1172/JCI174981.

TGF-β drives differentiation of intraepithelial mast cells in inflamed airway mucosa.

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PMID: 39744947 PMC: 11684809. DOI: 10.1172/JCI186337.

From the bench to the clinic: basophils and type 2 epithelial cytokines of thymic stromal lymphopoietin and IL-33.

Obata-Ninomiya K, Jayaraman T, Ziegler S Clin Transl Immunology. 2024; 13(12):e70020.

PMID: 39654685 PMC: 11626414. DOI: 10.1002/cti2.70020.

Interleukin-33-activated basophils promote asthma by regulating Th2 cell entry into lung tissue.

Schuijs M, Gomez C, Bick F, Van Moorleghem J, Vanheerswynghels M, van Loo G J Exp Med. 2024; 221(12).

PMID: 39297875 PMC: 11413418. DOI: 10.1084/jem.20240103.

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