Apoptotic cells ameliorate chronic intestinal inflammation by enhancing regulatory B-cell function

Area of Science:

• Immunology
• Gastroenterology

Background:

• Apoptotic cells (ACs) play a role in immune homeostasis, but their function in intestinal inflammation is poorly understood.
• Immune dysregulation is central to inflammatory bowel disease (IBD).

Purpose of the Study:

• To investigate the role of ACs in modulating intestinal inflammation and immune responses.
• To explore the potential therapeutic mechanisms of ACs in chronic colitis.

Main Methods:

• Adoptive transfer model of chronic colitis in severe combined immunodeficient mice.
• Administration of ACs with or without B cells or regulatory B cell (Breg)-depleted B cells.
• Assessment of colitis severity and cytokine production.
• Studies in milk fat globule-epidermal growth factor 8 knockout mice to assess phagocytosis.

Main Results:

• AC administration significantly reduced chronic colitis severity when whole B cells were cotransferred.
• The protective effect of ACs was lost in the absence of B cells or in the presence of Breg-depleted B cells.
• ACs induced splenic B cells to increase interleukin-10 (IL-10) secretion in a phagocytosis-dependent manner.

Conclusions:

• ACs exert a protective effect in chronic colitis specifically in the presence of B cells.
• ACs promote the development of IL-10-producing Bregs, suggesting a novel therapeutic mechanism.
• ACs may contribute to the anti-inflammatory effects of granulocyte/monocyte apheresis for IBD treatment.