Chapter 9 : Paneth Cells in Innate Immunity and Intestinal Inflammation

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Paneth Cells in Innate Immunity and Intestinal Inflammation, Page 1 of 2

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Paneth cells are specialized intestinal epithelial cells found mainly in the crypts of the small intestine. Paneth cells should be viewed as provisional until they can be confirmed by more specific markers. The presence of antimicrobial proteins in Paneth cells, which are secreted in response to bacterial products, implicates these cells in host defense against infection as part of the innate immune system. Paneth cells are present in the fetal intestine, although numbers are low at birth and increase postnatally, independently of the presence of intestinal microorganisms. The functions of Paneth cells are largely surmised from their repertoire of expressed genes, while direct experimentation has also confirmed a definite role in protection against enteric bacterial infection. In zinc deficiency, Paneth cell morphology is altered, and although metallothionein declines to undetectable levels in most epithelial cells, it can still be detected in the cytoplasm of Paneth cells. The location of Paneth cells adjacent to the stem cell zone of the small intestinal crypts has led to speculation that they play some role in maintaining stem cell function. Necrotizing enterocolitis (NEC) is probably triggered by intestinal infection, and inflammation and ischemia localized to the terminal ileum are prominent pathological features. Expression of antimicrobial genes, and experimental studies showing that Paneth cells respond to bacterial products and are required for enteric host defense, establish them as a significant component of innate immunity in the intestine.

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9

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Image of FIGURE 1

Paneth cells in the small intestinal epithelium. (a) Schematic diagram showing the relationship of crypts to villi and the position of Paneth cells in the base of the crypts. Numerous crypts supply absorptive enterocytes to each villus, which is the major surface for digestion and absorption of nutrients. (b) Cross-sectional diagram showing the relationship of Paneth cells to other cells in the crypt epithelium. Paneth cells occupy the most basal position and migrate toward the base as they differentiate and mature. Stem cells are probably located immediately adjacent to the Paneth cells, and the other intestinal epithelial cell types differentiate and migrate toward the lumen of the intestine and the opening of the crypt. The ultrastructure of Paneth cells is also depicted diagrammatically, showing the prominent rough endoplasmic reticulum, nucleus, Golgi apparatus, and secretory vesicles.

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9
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Image of FIGURE 2

Schematic view of Paneth cell gene expression.The putative functions of various Paneth cell products are depicted. Antibacterial products are secreted apically, where they function to regulate the population of microorganisms in the intestinal lumen. Guanylin released apically may stimulate secretion of chloride ions and water from crypt enterocytes, which express guanylin receptors on their luminal surface. Cytokines and growth factors may be released apically or basolaterally and probably act on adjacent cells in the epithelium and lamina propria. Products such as PLA may be released both apically and basolaterally, and they may be secreted in sufficient amounts to enter the circulation. Cell surface receptors on the Paneth cell membrane may mediate interactions with the products of enteric neurons, inflammatory and immune cells, and bacterial products. PGN, peptidoglycan; 5HT, 5-hydroxy tryptamine; LTA, lipoteichoic acid; VIP, vasoactive intestinal peptide.

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9
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Image of FIGURE 3

Hypothetical model for the pathogenesis of NOD2-mediated Crohn's disease. (a) In the normal intestinal epithelium, Paneth cells respond to microbial stimulation by secreting antibacterial substances that promote a normal balance of intestinal commensals and suppress the growth of pathogens. (b) Defects in the ability of Paneth cells to respond to bacterial stimulation (for example, caused by inherited mutations in the gene) may allow pathogenic bacteria to establish themselves in the intestine. Such bacteria, in turn, may induce inflammation by interaction with epithelial cells and leukocytes, and Paneth cells may exacerbate the resulting pathology by secreting proinflammatory mediators.

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9
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Generic image for table

Paneth cell gene expression

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9
Generic image for table

Putative Paneth cell functions

Citation: Keshav S. 2004. Paneth Cells in Innate Immunity and Intestinal Inflammation, p 171-196. In Kaufmann S, Medzhitov R, Gordon S (ed), The Innate Immune Response to Infection. ASM Press, Washington, DC. doi: 10.1128/9781555817671.ch9

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