The multifaceted Paneth cell

Porter, Edith; Bevins, Charles L.; Ghosh, Dipankar; Ganz, Tomas

doi:10.1007/s00018-002-8412-z

Cited by 358 publications

(295 citation statements)

References 179 publications

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“…Besides demonstrating broad anti-microbial properties, defensins have chemokine properties as well (28). The ␣-defensins, HD5 and HD6, are expressed by Paneth cells (29), and either whole bacteria or PAMPs such as LPS, LTA, and muramyl dipeptide stimulate release of defensins (30) …”

Section: Secretion Of Anti-microbial Peptidesmentioning

confidence: 99%

TLR Signaling in the Gut in Health and Disease

Abreu

Fukata

Arditi

2005

The Journal of Immunology

527

377

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The human intestine has evolved in the presence of diverse enteric microflora. TLRs convert the recognition of pathogen-associated molecules in the gut into signals for anti-microbial peptide expression, barrier fortification, and proliferation of epithelial cells. Healing of injured intestinal epithelium and clearance of intramucosal bacteria require the presence of intact TLR signaling. Nucleotide oligomerization domain (Nod)1 and Nod2 are additional pattern recognition receptors that are required for defense against invasive enteric pathogens. Through spatial and functional localization of TLR and Nod molecules, the normal gut maintains a state of controlled inflammation. By contrast, patients with inflammatory bowel disease demonstrate inflammation in response to the normal flora. A subset of these patients carry polymorphisms in TLR and CARD15/NOD2 genes. A better understanding of the delicate regulation of TLR and Nod molecules in the gut may lead to improved treatment for enteric infections and idiopathic inflammatory bowel diseases.

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Section: Secretion Of Anti-microbial Peptidesmentioning

confidence: 99%

TLR Signaling in the Gut in Health and Disease

Abreu

Fukata

Arditi

2005

The Journal of Immunology

527

377

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“…The third model proposes that mutations in NOD2 may result in altered mucosal host-microbe interactions (13). Nod2 is highly expressed in Paneth cells, epithelial cells of the intestinal crypts of Lieberkühn that govern innate immune responses through the secretion of antibacterial proteins and peptides such as α-defensins (22)(23)(24). CD-associated NOD2 mutations primarily predispose to the development of small intestinal (ileal) lesions, corresponding to the location of Paneth cells (25).…”

mentioning

confidence: 99%

Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

Biswas

Liu

Hao

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

148

140

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Mutations in the NOD2 gene are strong genetic risk factors for ileal Crohn’s disease. However, the mechanism by which these mutations predispose to intestinal inflammation remains a subject of controversy. We report that Nod2 -deficient mice inoculated with Helicobacter hepaticus , an opportunistic pathogenic bacterium, developed granulomatous inflammation of the ileum, characterized by an increased expression of Th1-related genes and inflammatory cytokines. The Peyer’s patches and mesenteric lymph nodes were markedly enlarged with expansion of IFN-γ–producing CD4 and CD8 T cells. Rip2 -deficient mice exhibited a similar phenotype, suggesting that Nod2 function likely depends on the Rip2 kinase in this model. Transferring wild-type bone marrow cells into irradiated Nod2 -deficient mice did not rescue the phenotype. However, restoring crypt antimicrobial function of Nod2 -deficient mice by transgenic expression of α-defensin in Paneth cells rescued the Th1 inflammatory phenotype. Therefore, through the regulation of intestinal microbes, Nod2 function in nonhematopoietic cells of the small intestinal crypts is critical for protecting mice from a Th1-driven granulomatous inflammation in the ileum. The model may provide insight into Nod2 function relevant to inflammation of ileal Crohn’s disease.

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“…I ntestinal epithelial cells (IEC) 3 must coexist with a high density of diverse bacteria. Protection against these bacteria exists on multiple levels.…”

mentioning

confidence: 99%

“…The first level of protection is the impermeability of the intestinal epithelial barrier. In addition to serving as a protective barrier, the epithelium plays an active role in the intestinal immune response through its secretion of inflammatory cytokines, chemokines, and antimicrobial peptides (1)(2)(3)(4). In the absence of pathogens, the intestinal epithelium maintains a controlled state of inflammation, whereas in the presence of a pathogen, acute inflammatory cells are recruited to the lamina propria and epithelium.…”

mentioning

confidence: 99%

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

Vora¹,

Youdim²,

Thomas³

et al. 2004

The Journal of Immunology

319

224

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The intestinal epithelium serves as a barrier to the intestinal flora. In response to pathogens, intestinal epithelial cells (IEC) secrete proinflammatory cytokines. To aid in defense against bacteria, IEC also secrete antimicrobial peptides, termed defensins. The aim of our studies was to understand the role of TLR signaling in regulation of β-defensin expression by IEC. The effect of LPS and peptidoglycan on β-defensin-2 expression was examined in IEC lines constitutively or transgenically expressing TLRs. Regulation of β-defensin-2 was assessed using promoter-reporter constructs of the human β-defensin-2 gene. LPS and peptidoglycan stimulated β-defensin-2 promoter activation in a TLR4- and TLR2-dependent manner, respectively. A mutation in the NF-κB or AP-1 site within the β-defensin-2 promoter abrogated this response. In addition, inhibition of Jun kinase prevents up-regulation of β-defensin-2 protein expression in response to LPS. IEC respond to pathogen-associated molecular patterns with expression of the antimicrobial peptide β-defensin-2. This mechanism may protect the intestinal epithelium from pathogen invasion and from potential invaders among the commensal flora.

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The multifaceted Paneth cell

Cited by 358 publications

References 179 publications

TLR Signaling in the Gut in Health and Disease

TLR Signaling in the Gut in Health and Disease

Induction and rescue of Nod2-dependent Th1-driven granulomatous inflammation of the ileum

β-Defensin-2 Expression Is Regulated by TLR Signaling in Intestinal Epithelial Cells

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