Decreased Lamina Propria Effector Cell Responsiveness to Interleukin-10 in Ileal Crohn's Disease

Colpaert, Stefaan; Vanstraelen, Kathleen; Liu, Zhanju; Penninckx, Freddy; Geboes, Karel; Rutgeerts, Paul; Ceuppens, Jan L.

doi:10.1006/clim.2001.5149

Cited by 15 publications

(9 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…or s.c. administration of IL-10 to patients with active CD or ulcerative colitis gave unclear results on the therapeutic efficacy of IL-10 treatment (41)(42)(43)(44)(45)(46). Several reasons can account for the overall failure of IL-10 therapy to treat inflammatory mucosal diseases, including an inappropriate route of administration, the short serum half-life of IL-10, and its pleiotropic activities (47). The current study has important implications for an IL-10-based therapy for CD.…”

Section: Discussionmentioning

confidence: 88%

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gianfrani

Levings

Sartirana

et al. 2006

The Journal of Immunology

125

View full text Add to dashboard Cite

Celiac disease (CD) results from a permanent intolerance to dietary gluten and is due to a massive T cell-mediated immune response to gliadin, the main component of gluten. In this disease, the regulation of immune responses to dietary gliadin is altered. Herein, we investigated whether IL-10 could modulate anti-gliadin immune responses and whether gliadin-specific type 1 regulatory T (Tr1) cells could be isolated from the intestinal mucosa of CD patients in remission. Short-term T cell lines were generated from jejunal biopsies, either freshly processed or cultured ex vivo with gliadin in the presence or absence of IL-10. Ex vivo stimulation of CD biopsies with gliadin in the presence of IL-10 resulted in suppression of Ag-specific proliferation and cytokine production, indicating that pathogenic T cells are susceptible to IL-10-mediated immune regulation. T cell clones generated from intestinal T cell lines were tested for gliadin specificity by cytokine production and proliferative responses. The majority of gliadin-specific T cell clones had a Th0 cytokine production profile with secretion of IL-2, IL-4, IFN-γ, and IL-10 and proliferated in response to gliadin. Tr1 cell clones were also isolated. These Tr1 cells were anergic, restricted by DQ2 (a CD-associated HLA), and produced IL-10 and IFN-γ, but little or no IL-2 or IL-4 upon activation with gliadin or polyclonal stimuli. Importantly, gliadin-specific Tr1 cell clones suppressed proliferation of pathogenic Th0 cells. In conclusion, dietary Ag-specific Tr1 cells are present in the human intestinal mucosa, and strategies to boost their numbers and/or function may offer new therapeutic opportunities to restore gut homeostasis.

show abstract

Section: Discussionmentioning

confidence: 88%

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gianfrani

Levings

Sartirana

et al. 2006

The Journal of Immunology

125

View full text Add to dashboard Cite

show abstract

“…24 In CD patients, there does not appear to be an IL10 deficiency in the ileum or in peripheral blood. 33 In the diseased ileum, IL10 does not downregulate proinflammatory cytokines and in fact may lead to increased TNFa production. 33 The explanation for these observations is not as yet clear but may involve interleukin-12 acting synergistically with IL10 in the inflamed tissue sites, but not in normal specimens.…”

Section: Discussionmentioning

confidence: 99%

“…33 In the diseased ileum, IL10 does not downregulate proinflammatory cytokines and in fact may lead to increased TNFa production. 33 The explanation for these observations is not as yet clear but may involve interleukin-12 acting synergistically with IL10 in the inflamed tissue sites, but not in normal specimens. Alternatively, CD patients may possess an abnormality within the IL10 pathway further downstream (the IL10 receptor).…”

Section: Discussionmentioning

confidence: 99%

TNF and IL10 SNPs act together to predict disease behaviour in Crohn's disease

Fowler¹,

Eri²,

Hume³

et al. 2005

Journal of Medical Genetics

View full text Add to dashboard Cite

“…The reduction in circulating β 7 + and β 7 – IL‐10 producing T cells in Crohn's disease may be due to selective recruitment of IL‐10 producing T cells into intestinal tissue in an attempt to control inflammation. Expression of mRNA for IL‐10 has been shown to be elevated in the mucosa of IBD patients compared with healthy controls [37,38] and lymphocytes cells extracted from mucosal tissue of Crohn's disease patients produced normal levels of IL‐10 in vitro [39]. There may be defective signalling by IL‐10 rather than a lack of production and supporting this concept, cells extracted from the mucosa of IBD patients are deficient in their response to IL‐10 [39].…”

Section: Discussionmentioning

confidence: 99%

Quantitative and functional characteristics of intestinal-homing memory T cells: analysis of Crohn's disease patients and healthy controls

Hart

Kamm

Knight

et al. 2003

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SUMMARYCirculating memory T cells can be subdivided on the basis of b 7 integrin expression. The b 7+ population contains cells primed in the intestine capable of homing back to the gut. We hypothesized that cytokine production by b 7 + memory T cells reflects the specialized mucosal compartment in which they were primed. Flow cytometry of whole blood was used to assess numbers of b 7 + ( b 7 hi and b 7 int ) and b 7 -memory T cells and their production of Th1 and regulatory cytokines in healthy controls and Crohn's disease patients. In controls, b 7 + and b 7 -memory T cells displayed a similar qualitative profile of cytokine production but the b 7 + population was enriched for cytokine-producing effector cells. In addition, the b 7 hi population contained more cytokine-producing cells than the b 7 int population, suggesting a gradient of cytokine production based on b 7 integrin expression. In active Crohn's disease, there was altered expression of b 7 integrin with a decrease in intestinal-homing memory T cells and an increase in systemic memory T cells. Furthermore, there was a selective loss of IL-10 and increase in TGF-b in both b 7 + and b 7 -memory T cell subsets which may contribute to the pathogenesis of the inflammatory process in Crohn's disease.

show abstract

Decreased Lamina Propria Effector Cell Responsiveness to Interleukin-10 in Ileal Crohn's Disease

Cited by 15 publications

References 41 publications

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

Gliadin-Specific Type 1 Regulatory T Cells from the Intestinal Mucosa of Treated Celiac Patients Inhibit Pathogenic T Cells

TNF and IL10 SNPs act together to predict disease behaviour in Crohn's disease

Quantitative and functional characteristics of intestinal-homing memory T cells: analysis of Crohn's disease patients and healthy controls

Contact Info

Product

Resources

About