Epithelial NELF guards intestinal barrier function to ameliorate colitis by maintaining junctional integrity

Area of Science:

• Molecular Biology
• Gastroenterology
• Immunology

Background:

• Intestinal epithelial cells (IECs) require transcriptional programs for mucosal barrier function.
• The role of transcriptional elongation mechanisms in IEC barrier function is largely unknown.

Purpose of the Study:

• To investigate the role of the Negative Elongation Factor (NELF) complex in IEC homeostasis and barrier function.
• To determine the impact of NELF deficiency on intestinal epithelial integrity and inflammation.

Main Methods:

• Genetic and genomic approaches were used to study IEC-intrinsic NELF complex function.
• Gene expression analysis and in vivo models of epithelial damage and colitis were employed.

Main Results:

• NELF directly occupies gene loci, sustaining expression of junctional integrity genes.
• NELF deficiency in IECs leads to reduced expression of junction-related genes.
• Epithelial NELF deficiency results in increased IEC necroptosis and impaired barrier function due to microbial invasion.
• NELF-deficient mice show exacerbated intestinal inflammation and permeability in a colitis model.

Conclusions:

• The IEC-intrinsic NELF complex is critical for maintaining epithelial homeostasis and mucosal barrier function.
• Transcriptional elongation is a key regulatory step in defining the IEC transcriptome and protecting against intestinal damage.
• NELF plays a protective role against intestinal inflammation and barrier disruption.