T cells regulate intestinal motility and shape enteric neuronal responses to intestinal microbiota

Area of Science:

• Gastroenterology
• Immunology
• Neuroscience

Background:

• Intestinal homeostasis relies on the gut microbiota, immune system, and enteric nervous system (ENS).
• The precise mechanisms of their interaction remain unclear.

Purpose of the Study:

• To investigate how gut microbiota and T cells regulate intestinal transit, enteric neurogenesis, and neuronal density.
• To elucidate the role of cytokines IL-1β and IL-17A in these processes.

Main Methods:

• Comparison of wildtype and T-cell deficient germ-free mice colonized with specific pathogen-free (SPF) microbiota, conventionally raised SPF, or segmented filamentous bacteria (SFB).
• Assessment of small intestinal transit, enteric neuronal density, neurogenesis markers (Sox2, nestin), immune cell populations (Th17, Treg), and cytokine levels (IL-1β, IL-17A).
• Intervention using IL-1β and IL-17A neutralization.

Main Results:

• SPF microbiota increased small intestinal transit in a T cell-dependent manner.
• Both SPF and SFB microbiota increased neuronal density and stimulated enteric neurogenesis, with T cell-dependency varying by gut region.
• SPF colonization elevated Th17 cells and Treg cells, alongside increased IL-1β and IL-17A levels.
• Neutralization of IL-1β and IL-17A impacted microbiota-mediated neurogenesis but not motility.

Conclusions:

• Gut microbiota and T cells orchestrate intestinal physiology through complex interactions.
• Specific cytokines, IL-1β and IL-17A, are key mediators of microbiota-induced enteric neurogenesis.
• These findings offer novel insights into the microbiota-neuroimmune axis governing gut function.