Journal Article Ppublish
PubMed: 40091637 DOI: 10.5607/en24016
Neuroinflammation in Adaptive Immunodeficient Mice with Colitis-like Symptoms.
Exp Neurobiol 34(1):34-47
Authors: Sung Hee Park, Junghwa Kang, Ji-Young Lee, Jeong Seon Yoon, Sung Hwan Hwang, Ji Young Lee, Deepak Prasad Gupta, Il Hyun Baek, Ki Jun Han, Gyun Jee Song
Affiliations
- Translational Brain Research Center, International St. Mary's Hospital, Catholic Kwandong University, Incheon 22711, Korea.
- Research & Development, IMMUNISBIO CO. Ltd. Incheon 22711, Korea.
- Department of Internal Medicine, Catholic Kwandong University College of Medicine, International St. Mary's Hospital, Incheon 22711, Korea.
- Translational Brain Research Center, International St. Mary's Hospital, Catholic Kwandong University, Incheon 22711, Korea. Department of Medical Science, Catholic Kwandong University, Gangneung 25601, Korea.
Abstract
Emerging evidence suggests that systemic inflammation may play a critical role in neurological disorders. Recent studies have shown the connection between inflammatory bowel diseases (IBD) and neurological disorders, revealing a bidirectional relationship through the gut-brain axis. Immunotherapies, such as Treg cells infusion, have been proposed for IBD. However, the role of adaptive immune cells in IBD-induced neuroinflammation remains unclear. In this study, we established an animal model for IBD in mice with severe combined immune-deficient (SCID), an adaptive immune deficiency, to investigate the role of adaptive immune cells in IBD-induced neuroinflammation. Mice were fed 1%, 3%, or 5% dextran sulfate sodium (DSS) for 5 days. We measured body weight, colon length, disease activity index (DAI), and crypt damage. Pro-inflammatory cytokines were measured in the colon, while microglial morphology, neuronal count, and inflammatory cytokines were analyzed in the brain. In the 3% DSS group, colitis symptoms appeared at day 7, with reduced colon length and increased crypt damage showing colitis-like symptoms. By day 21, colon length and crypt damage persisted, while DAI showed recovery. Although colonic inflammation peaked at day 7, no significant increase in inflammatory cytokines or microglial hyperactivation was observed in the brain. By day 21, neuroinflammation was detected, albeit with a slight delay, in the absence of adaptive immune cells. The colitis-induced neuroinflammation model provides insights into the fundamental immune mechanisms of the gut-brain axis and may contribute to developing immune cell therapies for IBD-induced neuroinflammation.
MeSH
Cytokines, Cells, Colitis, Brain, Colon, Signs And Symptoms, Therapeutics, Nervous System Diseases