Transcriptomics

Dataset Information

0

Tuft cell-produced cysteinyl leukotrienes and IL-25 synergistically promote lung type 2 inflammation


ABSTRACT: Aeroallergen sensing by airway epithelial cells can trigger pathogenic immune responses leading to chronic type 2 inflammation, the hallmark of airway diseases such as asthma. Airway tuft cells are specialized chemosensory epithelial cells and the dominant source of the epithelial cytokine IL-25 in the trachea and of cysteinyl leukotrienes (CysLTs) in the naïve murine nasal mucosa. How IL-25 and CysLTs might cooperatively promote type 2 inflammation in the airways has not been clarified. Here, we showed that inhalation of LTC4 in combination with a subthreshold dose of IL-25 led to dramatic synergistic induction of type 2 inflammation throughout the lungs, causing rapid eosinophilia, inflammatory type 2 innate lymphoid cell (ILC2) proliferation and type 2 cytokine production, dendritic cell (DC) and CD4+ T cell recruitment and goblet cell hyperplasia. While lung eosinophilia was dominantly mediated through the classical CysLT receptor CysLT1R, type 2 cytokines and activation of innate immune cells required signaling through both CysLT1R and CysLT2R. Tuft cell-specific deletion of Ltc4s, the terminal enzyme required for CysLT production, reduced lung inflammation and the systemic immune response after inhalation of the mold aeroallergen Alternaria; this effect was further enhanced by concomitant blockade of IL-25. Our findings identified a potent synergy of CysLTs and IL-25 downstream of aeroallergen-trigged activation of airway tuft cells leading to a highly polarized type 2 immune response and further implicate airway tuft cells as powerful modulators of type 2 immunity in the lungs.

ORGANISM(S): Mus musculus

PROVIDER: GSE188820 | GEO | 2021/12/25

REPOSITORIES: GEO

Dataset's files

Source:
Action DRS
Other
Items per page:
1 - 1 of 1

Similar Datasets

2024-07-25 | GSE241625 | GEO
2018-05-05 | GSE114067 | GEO
2018-05-19 | GSE114668 | GEO
2024-06-24 | GSE268129 | GEO
2024-05-02 | GSE262198 | GEO
2020-08-24 | GSE145827 | GEO
2020-08-24 | GSE145828 | GEO
2020-08-24 | GSE145829 | GEO
2022-09-14 | GSE197162 | GEO
2022-09-14 | GSE197156 | GEO