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Paneth Cells

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Paneth Cells

Paneth Cells are specialized cells that play a major role in the Innate Immunity of the Gastrointestinal (GI) Tract. Paneth Cells are located at the bottom of Intestinal Crypts and release antimicrobial proteins, called Alpha-Defensins (ex. HD-5).[1][2]

Paneth Cells are derived from multipotent Stem Cells (SC) located within Intestinal Crypts.[1][2]

Paneth Cell Function and Crohn's Disease


Paneth Cells are thought to play a role in Crohn's Disease. Patients with Ileal Crohn's Disease can have reduced alpha-defensin (HD-5 and HD-6) levels.

Lowered Alpha-defensin secretion from Paneth Cells in Ileal Crohn's Disease patients is correlated with Nod2 / Card15 Gene and/or Autophagy-Related 16 Like-1 (ATG16L1) gene mutations.[1][2]

Lowered alpha-defensin levels may be due, in part, to decreased TCF-4 transcription factor expression. Lower TCF-4 is found in pediatric and adult Ileal Crohn's Disease.

TCF-4 and Wnt signaling affect numbers of Paneth Cells (experiments in mice).

Reduced numbers of Paneth Cells in the GI Tract increase susceptibility to infection.

Alpha-defensins control not only the numbers of microbes present in the GI Tract but also help regulate the type (experiments in mice).[1][2]

Crohn's Disease in Children


- Approximately 25% of Crohn's Disease cases are diagnosed in children.

- Tissue samples from children with Crohn's Disease have higher Interleukin 8 (IL8) expression than tissue samples from controls.

- Pediatric - onset Crohn's Disease is typically more aggressive than late - onset Crohn's Disease and more often results in stricturing or penetrating complications.

- Crohn's Disease in children is typically of Ileocolonic - type, whereas late-onset Crohn's Disease patients more often have symptoms of Ileal location.

- Crohn's Disease symptoms in children are thought to be weighted more heavily on genetic factors than effects from environmental exposures.

Paneth Cell Defect Affects Crohn's Disease in Children and Adults

- In children and adults with Ileal Crohn's Disease (iCD) Paneth Cells can secrete significantly less HD-5 than in people who do not have Crohn's Disease.[3] The HD-5 gene expression was even more significantly reduced in patients with iCD and NOD2 / CARD15 Gene mutation.

- Lowered HD-5 expression alone is not correlated with inflammation.[3] However, certain IBD gene mutations can induce both Inflammation and reduced HD-5 secretion.

- Mutations in XBP1 - X-box binding protein 1 can cause defective Paneth Cell responses in the GI Tract.

References


1. Beisner J, Stange EF and Wehkamp J. Paneth cell function. Implications in pediatric Crohn disease. Gut Microbes 2011; 2(1):47-51. http://www.landesbioscience.com/jour...nerGMIC2-1.pdf

2. Gersemann M, Stange EF and Wehkamp J. From intestinal stem cells to inflammatory bowel diseases. World J Gastroenterol. 2011;17(27): 3198–3203. http://www.ncbi.nlm.nih.gov/pmc/arti...JG-17-3198.pdf

3. Bevins CL, Stange EF, and Wehkamp J. Decreased Paneth cell defensin expression in ileal Crohn’s disease is independent of inflammation, but linked to the NOD2 1007fs genotype. Gut.2009; 58:882-883. http://gut.bmj.com/content/58/6/882.full.pdf+html

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