TACSTD2 upregulation is an early reaction to lung infection

Area of Science:

• Molecular biology
• Pulmonology
• Evolutionary biology

Background:

• The transmembrane glycoprotein Trop2, encoded by TACSTD2, is overexpressed in carcinomas.
• Despite its discovery in 1981 and recent antibody-drug conjugate approvals for cancer therapy, Trop2's physiological role remains unclear.
• Understanding Trop2's function is crucial for advancing cancer treatments and lung health.

Purpose of the Study:

• To investigate the evolutionary conservation and physiological function of TACSTD2/Trop2 in the lung.
• To determine the cellular sources and regulation of TACSTD2 expression in response to lung infection.
• To elucidate Trop2's potential role in lung epithelial barrier maintenance and regeneration.

Main Methods:

• Analysis of evolutionary conservation of TACSTD2 expression in vertebrate lungs.
• Bioinformatic analysis of publicly available transcriptomic datasets from infected lungs.
• Single-cell and subpopulation transcriptomic analysis to identify TACSTD2-expressing cells and induction patterns.

Main Results:

• TACSTD2/Trop2 expression is evolutionarily conserved across vertebrate lung tissues.
• TACSTD2 transcript levels significantly increase in lungs infected with various pathogens, predominantly viruses.
• Lung epithelial cells and progenitors are the primary source of TACSTD2 transcripts, with direct induction upon infection.

Conclusions:

• TACSTD2/Trop2 expression is a conserved response to lung infection in vertebrates.
• Increased Trop2 expression in lung epithelial cells may facilitate barrier function restoration and tissue regeneration.
• This finding provides new insights into the physiological roles of Trop2 beyond cancer.