IFNγ induces epithelial reprogramming driving CXCL11-mediated T cell migration.

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Interferon-gamma (IFNγ) has complex roles in intestinal immunity, acting as both anti-inflammatory and pro-inflammatory.
• Understanding how IFNγ directly impacts intestinal epithelial cells and subsequent immune cell behavior is crucial for managing gut inflammation.

Approach:

• Utilized a 3D co-culture system with human intestinal epithelial organoids to model the intestinal environment.
• Investigated the effects of IFNγ exposure on organoid transcriptional profiles and chemokine secretion.
• Assessed the impact of IFNγ-treated organoids on T cell migration and activation.

Key Points:

• IFNγ treatment induced a pro-inflammatory transcriptional shift in intestinal organoids, upregulating chemokines CXCL9, CXCL10, and CXCL11.
• Proteomic analysis confirmed the secretion of these chemokines by IFNγ-treated organoids.
• IFNγ-exposed organoids enhanced T cell migration in a CXCL11-dependent manner, without altering T cell activation.

Conclusions:

• IFNγ reprograms intestinal epithelia to promote a pro-inflammatory state.
• CXCL11 plays a significant role in mediating T cell recruitment to the inflamed intestine.
• Targeting CXCL11 presents a potential therapeutic strategy to inhibit T cell trafficking in intestinal inflammatory diseases.