Epithelial NF-κB shapes protective Treg cell responses to restrain intestinal inflammation.

Epithelial NF-κB activity promotes a protective Treg cell response that is crucial for resolving intestinal inflammation in colitis.

• Why it matters: Understanding how the intestinal epithelium influences immune responses is vital for developing therapies for inflammatory bowel diseases like ulcerative colitis, where immune regulation is disrupted.
• What they did: Using colonic biopsies from UC patients and mouse models, combined with single-cell RNA sequencing and secretome analysis, the study examined epithelial NF-κB-driven secretome and its role in immune cell recruitment and regulation.
• The result: Epithelial NF-κB promotes CCL22-dependent Treg cell recruitment and a tolerogenic cell state, with its activity being selectively pro-inflammatory in UC, highlighting a dynamic epithelial-immune communication axis that aids inflammation resolution.