Glucocorticoid induced group 2 innate lymphoid cell overactivation exacerbates experimental colitis

Area of Science:

• Immunology
• Gastroenterology
• Neuroscience

Background:

• Inflammatory bowel disease (IBD) involves immune system dysregulation.
• Anxiety is linked to IBD risk, potentially via the adaptive immune system.
• The impact of anxiety on innate immunity and IBD severity is not fully understood.

Purpose of the Study:

• To investigate how anxiety influences innate immunity and exacerbates IBD.
• To elucidate the mechanism linking anxiety, stress hormones, and colonic inflammation.

Main Methods:

• A murine model of acute wrap restraint stress (WRS) was used to simulate anxiety.
• Group 2 innate lymphoid cells (ILC2) activation and cytokine production were assessed.
• Levels of corticosterone (CORT), IL-6, TNF-α, IL-5, and IL-13 were measured.
• Dexamethasone (DEX) was used to mimic CORT effects, and the IL-13/STAT6 pathway was blocked.

Main Results:

• Anxiety (WRS) led to overactivated ILC2s, increased IL-5 and IL-13, and aggravated colitis.
• WRS mice showed greater weight loss, shorter colons, elevated IL-6 and TNF-α, and impaired barrier function.
• Elevated serum CORT levels were observed in WRS mice.
• DEX administration mimicked WRS effects, increasing ILC2 activity and colitis severity.
• Blocking the IL-13/STAT6 pathway ameliorated colitis in stressed and DEX-treated mice.

Conclusions:

• Anxiety-induced corticosterone overproduction drives ILC2 overactivation.
• Overactive ILC2s, stimulated by CORT, contribute to the development and severity of colitis.
• Targeting the IL-13/STAT6 pathway may offer therapeutic potential for anxiety-associated IBD.