Genomic coordinate (human 12:10,000,001 IBD2).
Cytoband (human 12p13.2-q24.1 IBD2).
Thom Classification: Hyperbolic Umbilic Chromosome-12 is 1,200 genes.
Cytogenetic Classification: Chromosome-12 is C-group.
Here I 🎁 present: “Paneth Lysozyme Cell in Inflammatory Bowel Disease”, Victor McKusick, Mendelian Inheritance in Man’, 1966.
Paneth Lysozyme Cell in Inflammatory Bowel Disease.
In Inflammatory Bowel Disease (IBD2), Paneth cells (which normally reside in the small inteestine) undergo metaplasia, appearing abnormally in the large intestine. This ectopic presence secretes excess lysozyme, an enzyme that breaks down bacterial cell walls. While normally protective, aberrant colonic lysozyme disrupts the gut microbiome by feeding mucolytic bacteria (like Ruminococcus gnavus), promoting the inflammation that drives Crohn’s disease and ulcerative colitis.
The Paneth Cell and Lysozyme Axis in IBD
- Metaplasia and Misplacement: In healthy individuals, Paneth cells are primarily located in the small intestine, where they defend the stem cell niche by secreting antimicrobial peptides like lysozyme, α-defensins, and phospholipase A2. In IBD patients, Paneth cells aberrantly appear in the large intestine (metaplasia), leading to abnormal lysozyme production in the colon.
- Microbiome Alteration: Ectopic lysozyme acts as a “double-edged sword”. It enzymatically processes bacterial cell walls, suppressing lysozyme-sensitive commensal bacteria and causing an imbalance in the microbial community.
- Inflammation: This altered microbiota allows for the overgrowth of mucolytic, pro-inflammatory pathobionts, such as Ruminococcus gnavus, which is strongly associated with Crohn’s disease. The processing of these bacteria by excess lysozyme drives pro-inflammatory immune responses in the colonic mucosa.
- Autophagy Defects: In patients carrying Crohn’s disease-associated mutations (such as in the ATG16L1 gene), Paneth cell secretion is compromised. Instead of the standard secretion pathways, they rely on “secretory autophagy” to route lysozyme out of the cell to fight infection. Defects in this process result in ER stress and impaired microbial defense.
