Epithelially Restricted Interferon Epsilon Protects Against Colitis.

Area of Science:

• Immunology
• Gastroenterology
• Cell Biology

Background:

• Type I interferon (T1IFN) signaling is essential for intestinal homeostasis.
• Interferon epsilon (IFN-ε), a novel T1IFN, is expressed in the female reproductive tract, protecting against pathogens.
• The function of IFN-ε in the intestine remained unstudied.

Purpose of the Study:

• To investigate the expression and function of IFN-ε in the intestinal epithelium.
• To determine the role of IFN-ε in maintaining intestinal homeostasis and regulating inflammation.

Main Methods:

• Characterization of IFN-ε expression in mouse and human intestinal tissues using immunostaining.
• Functional studies in a dextran sulfate sodium (DSS)-induced colitis mouse model.
• Utilized genetic knockout (IFN-ε-/-) mice and neutralizing antibodies against IFN-ε.

Main Results:

• IFN-ε is expressed in the intestinal epithelium of humans and mice, with expression decreasing during inflammation.
• IFN-ε limits intestinal inflammation in mouse models of colitis.
• IFN-ε deficiency leads to reduced regulatory T cell (Treg) frequencies, indicating a role in Treg maintenance.
• Transfer of wild-type Tregs ameliorates colitis in IFN-ε-/- mice, confirming IFN-ε's support of Treg function.

Conclusions:

• IFN-ε is expressed in the intestinal epithelium and plays a critical role in maintaining gut homeostasis.
• IFN-ε exhibits a protective function in the intestine, similar to its role in the female reproductive tract.
• IFN-ε demonstrates a protective role across multiple mucosal surfaces.