Altered Epithelial Cell Lineage Allocation and Global Expansion of the Crypt Epithelial Stem Cell Population Are Associated with Ileitis in SAMP1/YitFc Mice

Vidrich, Alda; Buzan, Jenny M.; Barnes, Sean; Reuter, Brian K.; Skaar, Kirstin; Ilo, Chibuzo; Cominelli, Fabio; Pizarro, Theresa T.; Cohn, Steven M.

doi:10.1016/s0002-9440(10)62326-7

Cited by 44 publications

(42 citation statements)

References 62 publications

(57 reference statements)

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“…Second, mucosal lymphocytes from the MLNs of SAMP mice proliferate and produce cytokines after stimulation with SPF-FA. Such immunobacterial interactions are expected in vivo, because SAMP mice display an early epithelial cell defect (24,25) that allows for a constant cross-talk between commensal bacteria and the gut immune system, which is in line with previous studies from both humans and mice (7,10,27). Third, our results indicate that different components of the mucosal immune system have unequal dependence on the presence of commensal bacteria.…”

Section: Discussionsupporting

confidence: 80%

“…In addition, there was selective suppression of the intestinal Th2 cytokines IL-5 and IL-13, whereas no effect was seen on others, i.e., IFN-␥. Finally, we have recently shown that SAMP mice display an epithelial cell defect that occurs before the development of histological injury (24). Because this defect is also present in GF mice (25), it therefore occurs independently of colonization by commensal flora.…”

Section: Discussionmentioning

confidence: 95%

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Commensal Bacteria Exacerbate Intestinal Inflammation but Are Not Essential for the Development of Murine Ileitis

Bamias

Okazawa

Rivera–Nieves

et al. 2007

The Journal of Immunology

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The pathogenesis of Crohn’s disease has been associated with a dysregulated response of the mucosal immune system against intraluminal Ags of bacterial origin. In this study, we have investigated the effects of germfree (GF) conditions in the SAMP1/YitFc murine model of Crohn’s disease-like ileitis. We show that the bacterial flora is not essential for ileitis induction, because GF SAMP1/YitFc mice develop chronic ileitis. However, compared with disease in specific pathogen-free (SPF) mice, ileitis in GF mice is significantly attenuated, and is associated with delayed lymphocytic infiltration and defective mucosal expression of Th2 cytokines. In addition, we demonstrate that stimulation with purified fecal Ags from SPF, but not GF mice leads to the generation of IL-4-secreting effector lymphocytes. This result suggests that commensal bacteria drive Th2 responses characteristic of the chronic phase of SAMP1/YitFc ileitis. Finally, adoptive transfer of CD4-positive cells from GF, but not SPF mice induces severe colitis in SCID recipients. These effects were associated with a decreased frequency of CD4+CD25+Foxp3+ T cells in the mesenteric lymph nodes of GF mice compared with SPF mice, as well as lower relative gene expression of Foxp3 in CD4+CD25+ T cells in GF mice. It is therefore apparent that, in the absence of live intraluminal bacteria, the regulatory component of the mucosal immune system is compromised. All together, our results indicate that in SAMP1/YitFc mice, bacterial flora exacerbates intestinal inflammation, but is not essential for the generation of the chronic ileitis that is characteristic of these mice.

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 95%

Commensal Bacteria Exacerbate Intestinal Inflammation but Are Not Essential for the Development of Murine Ileitis

Bamias

Okazawa

Rivera–Nieves

et al. 2007

The Journal of Immunology

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“…Indeed, the relationship between crypt hyperplasia and goblet cell depletion phenotypes observed in other models of intestinal inflammation appears to be complex: for example, the immune system-mediated pathology that occurs during murine helminth infections results in both crypt and goblet cell hyperplasia (2,34,35). Moreover, in SAMP1/YitFc mice which develop spontaneous Crohn's disease-like ileitis (72), inflammationinduced crypt elongation is associated with the expansion of secretory lineages, including Paneth and goblet cells (72). Taken together, these studies suggest that the mechanisms underlying the depletion of mature goblet cells during C. rodentium infection may involve processes that are independent of, but coordinated with, the induction of crypt hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen

et al. 2008

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The attaching and effacing (A/E) bacterial pathogens enteropathogenic Escherichia coli and enterohemorrhagic E. coli and the related mouse pathogen Citrobacter rodentium colonize their hosts' intestines by infecting the apical surfaces of enterocytes, subverting their function, and they ultimately cause diarrhea. Surprisingly, little is known about the interactions of these organisms with goblet cells, which are specialized epithelial cells that secrete the protective molecules Muc2 and trefoil factor 3 (Tff3) into the intestinal lumen. C. rodentium infection leads to dramatic goblet cell depletion within the infected colon, yet it is not clear whether C. rodentium infects goblet cells or if this pathology is pathogen or host mediated. As determined by immunostaining and PCR, both the number of goblet cells and the expression of genes encoding Muc2 and Tff3 were significantly reduced by day 10 postinfection. While electron microscopy and immunostaining revealed that C. rodentium directly infected a fraction of colonic goblet cells, C. rodentium localization did not correlate with goblet cell depletion. To assess the role of the host immune system in these changes, Rag1 knockout (KO) (Tand B-cell-deficient) mice were infected with C. rodentium. Rag1 KO mice did not exhibit the reduction in the number of goblet cells or in mediator (Muc2 and Tff3) expression observed in infected immunocompetent mice. However, reconstitution of Rag1 KO mice with T and B lymphocytes from C57BL/6 mice restored the goblet cell depletion phenotype during C. rodentium infection. In conclusion, these studies demonstrated that while colonic goblet cells can be subject to direct infection and potential subversion by A/E pathogens in vivo, it is the host immune system that primarily modulates the function of these cells during infection.Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) are food-and waterborne pathogens that are attaching and effacing (A/E) bacteria, a class of noninvasive enteric bacterial pathogens (49). These bacteria infect the apical surfaces of intestinal epithelial cells, causing a signature histopathology characterized by intimate attachment to the host plasma membrane and localized effacement of the brush border immediately surrounding the attached bacteria (16, 74). As a result of this infection and the resulting host inflammatory response, EPEC and EHEC cause severe diarrhea and other complications, leading to the death of hundreds of thousands of children worldwide each year (7,28,49

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“…Intermediate cells are rarely seen in normal adult intestinal epithelium, but they have been reported in cases of intestinal infection, inflammation, and inhibition of Notch signaling (36,39,42). The function of these secretory cells is not clear.…”

Section: A' A''mentioning

confidence: 99%

Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage

King

Mohiuddin

Dekaney

2013

American Journal of Physiology-Gastrointestinal and Liver Physi

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King SL, Mohiuddin JJ, Dekaney CM. Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage. Am J Physiol Gastrointest Liver Physiol 305: G151-G162, 2013. First published May 9, 2013 doi:10.1152/ajpgi.00441.2012.-Paneth cell numbers increase following intestinal damage, but mechanisms driving this process are not understood. We hypothesized that the increase in Paneth cell numbers is due to recruitment of cells from a preexisting pool of secretory progenitors. Mice were given a single injection of doxorubicin (Dox), and intestinal tissue was collected 0 -168 h after treatment. Paneth, goblet, and intermediate cells were counted and evaluated for cell morphology. Quantitative RT-PCR was used to measure expression of various genes associated with Paneth cell allocation and maturation. Paneth cells were birth dated using incorporation of thymidine analogs given before or after Dox. Staining revealed "intermediate" cells, which were rarely observed in control crypts but increased significantly in number 96 and 120 h after Dox treatment. Birth dating of intermediate cells 5 days after Dox treatment revealed that 24% of these cells took up thymidine analog given prior to Dox treatment and 36% took up thymidine analog given after Dox treatment. Quantitative RT-PCR demonstrated a significant increase in Spdef, Atoh1, Sox9, EphB3, Mist, Wnt5a, FGF-9, and FGF-18 mRNAs and a significant decrease in Indian hedgehog mRNA. Expansion of the Paneth cell compartment after Dox treatment is due to generation of new cells and recruitment of cells from an existing pool. These cells express Paneth and goblet biomarkers and are found only during repair. Expansion of these cells correlates temporally with reduced Indian hedgehog and increased FGF and Wnt mRNA. These findings are significant, as they provide a first step in understanding mechanisms of Paneth cell expansion during mucosal repair. Paneth cell; doxorubicin; intermediate cell PANETH CELLS ARE ONE OF FOUR differentiated cell lineages that arise from intestinal stem cells (ISC), and unlike the other three cell lineages found in small intestinal epithelium, they migrate toward and reside in the base of intestinal crypts (5, 6). Paneth cells are part of the innate mucosal immune system in the intestine and protect against microbial infection and overgrowth. Antimicrobial peptides, including cryptdins (␣-defensins), lysozyme, secretory phospholipase A 2 , and matrilysin [matrix metalloproteinase 7 (MMP-7)], are secreted from granules localized to the apical membrane of Paneth cells upon bacterial stimulation (2,25). At the crypt base, Paneth cells are adjacent to and intercalated among ISC and are, therefore, in an advantageous position to influence the stem cell microenvironment (5, 6). In addition to secreting numerous antimicrobial factors, Paneth cells synthesize and secrete factors that are capable of influencing proliferation and migration of intestinal epithelial cells, including EGF, granulocyte-macrophage colony-stimul...

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Altered Epithelial Cell Lineage Allocation and Global Expansion of the Crypt Epithelial Stem Cell Population Are Associated with Ileitis in SAMP1/YitFc Mice

Cited by 44 publications

References 62 publications

Commensal Bacteria Exacerbate Intestinal Inflammation but Are Not Essential for the Development of Murine Ileitis

Commensal Bacteria Exacerbate Intestinal Inflammation but Are Not Essential for the Development of Murine Ileitis

Modulation of Intestinal Goblet Cell Function during Infection by an Attaching and Effacing Bacterial Pathogen

Paneth cells expand from newly created and preexisting cells during repair after doxorubicin-induced damage

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