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Published on: December 16, 2021
Induction of Colonic M Cells during Intestinal Inflammation
Kaila M Bennett1, Erinn A Parnell2, Candice Sanscartier1
1Bioengineering Interdepartmental Graduate Program, School of Medicine, University of California, Riverside, Riverside, California; Division of Biomedical Sciences, School of Medicine, University of California, Riverside, Riverside, California.
Abstract:
Intestinal M (microfold) cells are specialized epithelial cells overlying lymphoid tissues in the small intestine. Unlike common enterocytes, M cells lack an organized apical brush border, and are able to transcytose microparticles across the mucosal barrier to underlying antigen-presenting cells. We found that in both the dextran sodium sulfate and Citrobacter rodentium models of colitis, significantly increased numbers of Peyer's patch (PP) phenotype M cells were induced at the peak of inflammation in colonic epithelium, often accompanied by loosely organized lamina propria infiltrates. PP type M cells are thought to be dependent on cytokines, including tumor necrosis factor (TNF)-α and receptor activator of nuclear factor kappa-B ligand; these cytokines were also found to be induced in the inflamed tissues. The induction of M cells was abrogated by anti-TNF-α blockade, suggesting that anti-TNF-α therapies may have similar effects in clinical settings, although the functional consequences are not clear. Our results suggest that inflammatory cytokine-induced PP type M cells may be a useful correlate of chronic intestinal inflammation.
Insights
Inflammation during colitis increases microfold (M) cells in the gut lining. Blocking tumor necrosis factor-alpha (TNF-α) reduced M cell induction, suggesting a potential therapeutic target for chronic intestinal inflammation.
Area of Science:
- Immunology
- Gastroenterology
- Cell Biology
Background:
- Intestinal M (microfold) cells are specialized epithelial cells facilitating antigen transport across the mucosal barrier.
- Unlike enterocytes, M cells lack a brush border and are crucial for immune surveillance in the gut.
- Their role in inflammatory conditions like colitis is not fully understood.
Purpose of the Study:
- To investigate the induction and regulation of Peyer's patch (PP) phenotype M cells in experimental colitis models.
- To explore the role of inflammatory cytokines, specifically tumor necrosis factor-alpha (TNF-α), in M cell differentiation during intestinal inflammation.
Main Methods:
- Utilized dextran sodium sulfate (DSS) and Citrobacter rodentium infection models to induce colitis in mice.
- Quantified M cell numbers in the colonic epithelium during peak inflammation.
- Assessed the expression of key cytokines (TNF-α and RANKL) in inflamed tissues.
- Investigated the effect of anti-TNF-α blockade on M cell induction.
Main Results:
- Significantly increased numbers of PP phenotype M cells were observed in the colonic epithelium of colitis models at the peak of inflammation.
- Induction of M cells correlated with increased levels of TNF-α and RANKL in inflamed tissues.
- Anti-TNF-α blockade effectively abrogated the induction of M cells, indicating TNF-α's critical role.
Conclusions:
- Inflammatory cytokines, particularly TNF-α, drive the induction of PP type M cells in the colonic epithelium during experimental colitis.
- Induced M cells may serve as a valuable correlate for assessing chronic intestinal inflammation.
- Anti-TNF-α therapies might influence M cell populations in clinical settings of intestinal inflammation, though functional consequences require further study.
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