A recent study exploring the dynamics of intestinal motility in inflammatory bowel disease sheds light on the adaptive immune system's crucial, segment-specific role in the gastrointestinal tract.
Conducted using a mouse model of dextran sulfate sodium (DSS)-induced colitis, the research revealed how adaptive lymphocytes shape motility patterns and inflammatory responses in the ileum and colon under both healthy and disease conditions. Published in The American Journal of Pathology, the research examined wild-type (WT) and immune-deficient Rag1-/- mice, which lack mature T and B lymphocytes, to compare intestinal motility and tissue damage across different regions of the gastrointestinal tract. DSS treatment, a widely used model of colitis, was used to simulate inflammatory bowel disease (IBD)-like inflammation.
The researchers documented segment-specific motility regulation. In the ileum, adaptive immunity reduced acetylcholine (ACh) sensitivity under normal conditions. During colitis, immune activity enhanced spontaneous contractions but also heightened cholinergic responsiveness, suggesting a compensatory mechanism for inflammation. In the proximal colon, adaptive lymphocyte deficiency increased contractility at baseline but reduced it during colitis. The mid-colon demonstrated heightened contractile responses during colitis in immune-deficient mice, highlighting a unique inflammatory susceptibility. In the distal colon, the loss of adaptive immunity decreased contractility and cholinergic responsiveness during inflammation.
Rag1-/- mice exhibited reduced tissue damage and inflammation markers, such as tumor necrosis factor (TNF)-alpha expression, during colitis compared to WT mice. These effects were region-dependent, with the colon showing more pronounced inflammation than the ileum, consistent with colitis's localized impact on the large intestine.
Adaptive immunity influenced the expression of acetylcholinesterase and muscarinic receptors (M2/M3), which regulate ACh breakdown and receptor sensitivity, respectively. This modulation varied by intestinal segment and was more pronounced during colitis.
Patients with IBD often experience motility disturbances, including diarrhea, constipation, and abdominal pain. While these symptoms are typically attributed to inflammation, this study underscored a direct role of adaptive immune cells in altering gut motility patterns.
The findings suggested that adaptive immunity modulates not only inflammatory responses but also the bioavailability of ACh, a key neurotransmitter in gut motility. The study highlighted potential therapeutic targets, such as acetylcholinesterase inhibitors, to enhance ACh availability and mitigate motility disturbances in IBD.
This research contributed to a growing understanding of the complex interplay between the immune system and gastrointestinal physiology. By delineating the segment-specific effects of adaptive lymphocytes, the researchers suggested the findings may open avenues for targeted interventions to address motility dysfunctions in IBD while mitigating systemic side effects.
Future studies should explore these mechanisms in human tissues to confirm their clinical relevance and evaluate how adaptive immunity influences long-term recovery and tissue repair in IBD, the authors wrote.
