Fasting-Refeeding Impacts Immune Cell Dynamics and Mucosal Immune Responses

Area of Science:

• Immunology
• Nutritional Science
• Gastroenterology

Background:

• Nutritional status influences immune responses, but the underlying mechanisms are unclear.
• Peyer's patches (PPs) are crucial inductive sites for gut immunity.

Purpose of the Study:

• To investigate how nutritional signals regulate immune cell dynamics and function in PPs.
• To understand the impact of fasting and refeeding on gut immune homeostasis.

Main Methods:

• Temporary fasting and refeeding protocols in a model system.
• Analysis of lymphocyte populations and cellular composition in PPs.
• Investigation of B cell migration patterns and chemokine expression (CXCL13).
• Assessment of oral immunization, antigen-specific IgA induction, and oral tolerance.

Main Results:

• Fasting reduced lymphocyte numbers by ~50% in PPs, with significant apoptosis of germinal center and IgA+ B cells.
• Naive B cells migrated from PPs to bone marrow during fasting and returned upon refeeding.
• Stromal cells upregulated CXCL13 expression during refeeding, recruiting naive B cells back to PPs.
• Fasting before oral immunization impaired IgA induction, oral tolerance, and exacerbated food antigen-induced diarrhea.

Conclusions:

• Nutritional signals critically regulate gut immune cell dynamics and function.
• Fasting disrupts gut immune homeostasis by altering lymphocyte composition and function.
• Refeeding restores lymphocyte numbers but not original composition, impacting adaptive immunity.