# Adenosine-Specific Transcriptional Programs in Murine Connective Tissue-Type Mast Cells

## TL;DR

This study identifies a unique set of genes activated by adenosine in mouse mast cells, revealing new pathways involved in inflammation.

## Contribution

The paper discovers a novel adenosine-specific transcriptional program in mast cells, including genes for new inflammatory mediators.

## Key findings

- 393 genes are uniquely regulated by adenosine in murine mast cells.
- Genes like transforming growth factor α and interleukin 7 are part of the adenosine-specific program.
- The program involves phosphoinositide signaling, vesicle trafficking, glycolysis, and cell cycle arrest.

## Abstract

Mast cells are tissue-resident
immune cells that are critical for
the pathogenesis of allergic and inflammatory disorders. Their physiological
functions include host defense against parasites and, more recently,
food quality control through antigen avoidance. The purine nucleoside
adenosine (ADO), like other mast cell activators, such as antigens
or Mrgprb2 agonists, increases intracellular Ca2+ concentration;
however, it fails to induce degranulation of preformed mediators when
applied to mast cells alone, and there is limited knowledge about
whether ADO evokes the de novo synthesis and release of inflammatory
mediators in tissue mast cells. An unbiased genome-wide analysis of
gene expression triggered by various mast cell activators should enable
the identification of the gene program specifically activated by ADO
in mast cells and thereby reveal new components of the associated
inflammatory responses. Here, we performed bulk RNA sequencing on
primary murine peritoneal mast cells (PMCs) representing connective
tissue mast cells. By comparing responses evoked by ADO stimulation
with those of the Mrgprb2 agonist compound 48/80 and antigens activating
FcεRI receptors, we identified 393 genes uniquely regulated
by ADO, including genes encoding the de novo synthesized mediators
transforming growth factor α and interleukin 7. Transcription
factor activity inference, protein classification, functional enrichment
analysis, protein interaction network analysis, and topology analysis
revealed a distinct ADO-specific transcriptional gene program involved
in phosphoinositide signaling, vesicle trafficking, glycolysis, mitochondrial
activity, and cell cycle arrest. The functional relevance of the identified
de novo synthesized mediators for ADO-evoked inflammatory reactions
can be evaluated in future studies.