The role of inflammation-induced mast cells in lung diseases

My proposal aims at deciphering the biology of inflammation-induced mast cells with the purpose of determining their role in allergic asthma and lung cancer. Inflammation-induced mast cells mature at mucosal sites from mast cell progenitors.

Inflammation-induced mast cells will be studied in the acute and resolution phase of allergic inflammation and during the progression into lung cancer. Our recent data suggest that they survive, and gain pro-tumorigenic features upon resolution of allergic inflammation.

A pilot experiment revealed mast cell progenitors accumulating in the lung with tumors, suggesting inflammation-induced mast cells in the tumor microenvironment. I will lead this 4-year project, which will be carried out experimentally by my group members.

The major part will be experiments involving mouse models of allergic asthma, lung cancer and lung metastasis, which will be studied using transgenic mice enabling inflammation-induced mast cells to be depleted.

The experiments will be analyzed by fluorescence microscopy, flow cytometry, determination of lung function decline, and CITE-seq sequencing.

In addition, collaborators from Uppsala University hospital will make relevant clinical material available for translational analyses that my group members will perform.

We hope this study will provide an increased understanding of the pathological events behind these diseases, and result in better therapeutic options and improved diagnosis and prognosis.