Enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with Crohn's disease

Nüssler, Natascha C.; Stange, Barbara; Hoffman, Rosemary A.; Schraut, Wolfgang H.; Bauer, Anthony J.; Neuhaus, P.

doi:10.1007/s004230050268

Cited by 18 publications

(16 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with the reported increase in CD31 CD81 IEL in the rectal mucosa of Crohn's disease patients (30) and enhanced cytolytic activity of these cells (31), IL10(2/2) mice treated with the control diet had the highest proportion of CD31 IEL, most of them also expressing the CD8 phenotype. This was associated with a high incidence of colitis.…”

Section: Discussionsupporting

confidence: 84%

Partial Replacement of Dietary (n-6) Fatty Acids with Medium-Chain Triglycerides Decreases the Incidence of Spontaneous Colitis in Interleukin-10–Deficient Mice

Mañé¹,

Pedrosa²,

Lorén³

et al. 2009

The Journal of Nutrition

View full text Add to dashboard Cite

Enteral nutrition has a primary therapeutic effect in active Crohn's disease. It is unknown which nutrient(s) account for this action, but a role for both the amount and type of dietary fat has been postulated. Some clinical and experimental data suggest that medium-chain triglycerides (MCT) may reduce intestinal inflammation. We aimed to assess the effect of replacing part of the dietary fat with MCT on the incidence and severity of colitis in interleukin (IL)-10(-/-) mice under specific pathogen-free conditions. Twenty-four IL-10(-/-) 4-wk-old mice were randomized to receive a control diet based on sunflower oil [(n-6) fatty acids (FA)] and an experimental isocaloric, isonitrogenous diet with 50% sunflower and 50% coconut oil (MCT diet). When the mice were 12 wk old, they were killed and the colon was examined for the presence of colitis, lymphocyte subpopulations and apoptosis, ex vivo cytokine production in supernatant of colon explants, toll-like receptor (TLR)-2 and TLR-9 mRNA, and FA profile in colonic tissue homogenates. Colitis incidence was lower in the IL-10(-/-) mice fed the MCT diet (1/12) than in the mice fed the control diet (8/12; P = 0.03). The histological damage score was also lower in the former (P < 0.0005). Feeding the MCT diet resulted in fewer total and apoptotic intraepithelial CD3+ and lamina propria CD3+CD4+ lymphocytes, as well as downregulated production of IL-6 and interferon-gamma, and reduced TLR-9 mRNA. We conclude that partial replacement of dietary (n-6) FA with MCT decreases the incidence of colitis in a model of spontaneous intestinal inflammation and provide experimental arguments for a possible primary therapeutic effect of MCT in human Crohn's disease.

show abstract

Section: Discussionsupporting

confidence: 84%

Partial Replacement of Dietary (n-6) Fatty Acids with Medium-Chain Triglycerides Decreases the Incidence of Spontaneous Colitis in Interleukin-10–Deficient Mice

Mañé¹,

Pedrosa²,

Lorén³

et al. 2009

The Journal of Nutrition

View full text Add to dashboard Cite

show abstract

“…In this context, our finding that in CrD and UC the number of CD8 ϩ CD11a ϩ NF-B ϩ cells is significantly increased compared with controls was interesting, confirming the previously described enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with CrD ( Fig. 6) (24).…”

Section: Cd4supporting

confidence: 77%

Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn’s Disease and Ulcerative Colitis

Berndt

Bartsch²,

Philipsen³

et al. 2007

The Journal of Immunology

View full text Add to dashboard Cite

Although Crohn’s disease (CrD) and ulcerative colitis (UC) share several clinical features, the mechanisms of tissue injury differ. Because the global cellular function depends upon the protein network environment as a whole, we explored changes in the distribution and association of mucosal proteins to define key events involved in disease pathogenesis. Endoscopic biopsies were taken from CrD, UC, and control colonic mucosa, and Multi-Epitope-Ligand-Cartographie immunofluorescence microscopy with 32 different Abs was performed. Multi-Epitope-Ligand-Cartographie is a novel, highly multiplexed robotic imaging technology which allows integrating cell biology and biomathematical tools to visualize dozens of proteins simultaneously in a structurally intact cell or tissue. In CrD, the number of CD3+CD45RA+ naive T cells was markedly increased, but only activated memory, but not naive, T cells expressed decreased levels of Bax, active caspase-3 or -8. In UC, only CD4+ T cells coexpressing NF-κB were caspase-8 and poly(ADP-ribose)-polymerase positive. Furthermore, the number of CD4+CD25+ T cells was elevated only in UC, whereas in CrD and controls, the number of these cells was similar. By using hub analysis, we also identified that the colocalization pattern with NF-κB+ and poly(ADP-ribose)-polymerase+ as base motifs distinguished CrD from UC. High-content proteomic analysis of the intestinal mucosa demonstrated for the first time that different T cell populations within the intestinal mucosa express proteins translating distinct biological functions in each form of inflammatory bowel disease. Thus, topological proteomic analysis may help to unravel the pathogenesis of inflammatory bowel disease by defining distinct immunopathogenic profiles in CrD and UC.

show abstract

“…intestinal mucosa of Crohn's disease patients, and it has been suggested that increased cytolytic activity of CD8 + T cells in the intraepithelial compartment of the patients may be involved in the induction of epithelial tissue damage (Nussler et al 2000, Honma et al 2001, Melgar et al 2002. The findings from studies in giardiasis demonstrating that CD8 + lymphocytes are implicated in brush border injury and malfunction are consistent with this hypothesis.…”

mentioning

confidence: 84%

Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction

2005

Mem. Inst. Oswaldo Cruz

View full text Add to dashboard Cite

show abstract

Enhanced cytolytic activity of intestinal intraepithelial lymphocytes in patients with Crohn's disease

Abstract: In Crohn's disease, the functional and phenotypic changes of T cells are limited to lymphocytes of the intestinal mucosa. Furthermore, it is conceivable that the increased cytolytic activity of IEL contributes to the tissue damage in this disease.

Cited by 18 publications

References 30 publications

Partial Replacement of Dietary (n-6) Fatty Acids with Medium-Chain Triglycerides Decreases the Incidence of Spontaneous Colitis in Interleukin-10–Deficient Mice

Partial Replacement of Dietary (n-6) Fatty Acids with Medium-Chain Triglycerides Decreases the Incidence of Spontaneous Colitis in Interleukin-10–Deficient Mice

Proteomic Analysis of the Inflamed Intestinal Mucosa Reveals Distinctive Immune Response Profiles in Crohn’s Disease and Ulcerative Colitis

Immunopathology of giardiasis: the role of lymphocytes in intestinal epithelial injury and malfunction

Contact Info

Product

Resources

About