Macrophage development and activation involve coordinated intron retention in key inflammatory regulators

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• Monocytes and macrophages are crucial for innate immunity.
• Intron retention (IR) is an understudied post-transcriptional regulatory mechanism.
• Understanding IR's role in immune cells is vital for innate immune response insights.

Purpose of the Study:

• To investigate the role of intron retention (IR) in monocyte and macrophage development and function.
• To identify specific IR events and their impact on key immune genes.
• To elucidate the dynamic regulation of IR during macrophage activation and polarization.

Main Methods:

• Illumina mRNA sequencing
• Nanopore direct cDNA sequencing
• Proteomics analysis

Main Results:

• Identified IR events affecting genes critical for macrophage development and function.
• Decreased IR correlated with increased expression of regulators for transcription, phagocytosis, and inflammation (e.g., ID2, IRF7, ENG, LAT).
• Demonstrated dynamic IR regulation during macrophage polarization and response to inflammatory stimuli, with rapid splicing of CXCL2 and NFKBIZ transcripts.

Conclusions:

• Intron retention is a key regulatory mechanism in innate immune cells.
• Dynamic IR programs control macrophage function and inflammatory responses.
• This study reveals novel molecular factors governing innate immunity.