Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?

Bas, Anna; Forsberg, Göte; Sjöberg, Veronika; Hammarström, Sten; Hernell, Olle; Hammarström, Marie‐Louise

doi:10.1136/gut.2007.125526

Cited by 9 publications

(6 citation statements)

References 28 publications

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“…Cryosections were stained as previously described with the modification that 1% Triton-X100 was included in the blocking buffer [10]. The antibodies used were mouse anti-human IL-17A monoclonal antibody (mAb) (clone BL-168, IgG1; BioLegend, San Diego, CA) and mouse anti-human Foxp3 mAb (clone236A/E7, IgG1; Abcam, Cambridge, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Intraepithelial T lymphocytes, particularly CD8 + cells, are the major contributors of IFN-γ and IL-10 in biopsies collected from CD patients with active disease at diagnosis while the relative contribution from T cells in the LP increases in active CD caused by challenge with gluten after a symptom-free period on gluten-free diet [4], [9]. Furthermore, children with CD have impaired capacity for extrathymic T cell receptor (TCR) rearrangement suggesting that the failure to establish tolerance to gluten is at least partly due to reduced capacity to generate T cells locally in the small intestinal mucosa [10].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Intestinal T-cell Responses in Celiac Disease – Impact of Celiac Disease Associated Bacteria

et al. 2013

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A hallmark of active celiac disease (CD), an inflammatory small-bowel enteropathy caused by permanent intolerance to gluten, is cytokine production by intestinal T lymphocytes. Prerequisites for contracting CD are that the individual carries the MHC class II alleles HLA-DQ2 and/or HLA-DQ8 and is exposed to gluten in the diet. Dysbiosis in the resident microbiota has been suggested to be another risk factor for CD. In fact, rod shaped bacteria adhering to the small intestinal mucosa were frequently seen in patients with CD during the “Swedish CD epidemic” and bacterial candidates could later be isolated from patients born during the epidemic suggesting long-lasting changes in the gut microbiota. Interleukin-17A (IL-17A) plays a role in both inflammation and anti-bacterial responses. In active CD IL-17A was produced by both CD8+ T cells (Tc17) and CD4+ T cells (Th17), with intraepithelial Tc17 cells being the dominant producers. Gluten peptides as well as CD associated bacteria induced IL-17A responses in ex vivo challenged biopsies from patients with inactive CD. The IL-17A response was suppressed in patients born during the epidemic when a mixture of CD associated bacteria was added to gluten, while the reverse was the case in patients born after the epidemic. Under these conditions Th17 cells were the dominant producers. Thus Tc17 and Th17 responses to gluten and bacteria seem to pave the way for the chronic disease with interferon-γ-production by intraepithelial Tc1 cells and lamina propria Th1 cells. The CD associated bacteria and the dysbiosis they might cause in the resident microbiota may be a risk factor for CD either by directly influencing the immune responses in the mucosa or by enhancing inflammatory responses to gluten.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intestinal T-cell Responses in Celiac Disease – Impact of Celiac Disease Associated Bacteria

et al. 2013

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“…Bas et al20 showed that patients with CD may fail to regulate T cell response to gluten because of an impaired capacity for extra-thymic T cell receptor gene rearrangement.…”

Section: Introductionmentioning

confidence: 99%

Celiac disease

Rubio–Tapia

Murray

2010

Current Opinion in Gastroenterology

139

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Purpose of review To summarize recent advances in celiac disease (CD) published between August 2008 and July 2009. Recent findings CD affects ~1% of most populations but remains largely unrecognized. In the last year, work has shown that the prevalence of CD has increased dramatically, not simply due to increased detection. Also, undiagnosed CD may be associated with increased mortality. Significant progress has been made in understanding how gliadin peptides can cross the intestinal border and access the immune system. New genetic loci and candidate genes that may contribute to the risk of CD and its overlap with type 1 diabetes mellitus have been identified. New deamidated gliadin peptides antibodies have better diagnostic accuracy over native gliadin-based tests. The inclusion of duodenal bulb biopsy specimens may increase the rate of CD detection. The spectrum of CD likely includes a minority of patients with mild enteropathy. A practical 7-item instrument may facilitate standardized evaluation of gluten-free diet adherence. Finally, refractory CD, whilst rare, is associated with a poor prognosis. Summary Celiac disease is a global health problem that requires a multidisciplinary and increasingly cooperative multinational research effort.

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“…The CD4+ T cells play an important role in tissue injury [50] and in lamina propria predominates the phenotype Th1 with production of cytokines in response to gluten stimulation [51] . Researches [52] showed that patients with CD may fail to regulate T cell response to gluten because of an impaired capacity for extra-thymic T cell receptor gene rearrangement. Th1 cells are abundant in the LP and responsible for the maintenance of a suitable environment for antibody production at the duodenal mucosa and for the cytotoxic activity of IELs in untreated CD patients [53] .…”

Section: Function Of the Cellsmentioning

confidence: 99%

Celiac disease: Participation of Cytokines and Other Factors in the Immune Response

Romero-Adrián¹

2016

JGDLF

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Celiac disease (CD) is an autoimmune enteropathy that affects 1% of most populations. Genetic, immunological and environmental factors (the intake of gluten) participate in the establishment and development of the disease. Cells and cytokines make a network of interactions leading to intestinal inflammatory process. IFN-γ is the most potent inducer of transglutaminasa2 (TG2) expressions, acts synergistically with TNF-α, and triggers the upregulation of HLA expression, the secretion of tissue-damaging Metalloproteinases (MMPs) from fibroblasts, the heightened cytotoxicity of Intraepithelial Lymphocytes (IELs) against enterocytes with increased apoptosis and villous flattening. IL-12 and IL-18 have an important suppressive effect on the induction of antigen-specific tolerance and provoke a more vigorous response on challenge. Upregulation of IL-15 expression by epithelial cells and Dendritic Cells (DCs) in the lamina propria seems to contribute to alter signalling properties of the CD8+ intraepithelial lymphocytes and provokes the resistance of human T cells to the suppression by regulatory T cells. IL-15 and IL-21 might also act in concert to disrupt local mechanisms of immune tolerance. Increased expressions of several Th17 related cytokines in patients with active CD have been demonstrated. IL-10 acts by interfering with antigen presentation and induces hyporesponsive in gliadin specific T cells. TGF-β1 expression increased have been observed in the lamina propria of children with intestinal villous atrophy, which appoint its importance in the pathogenesis of CD. In this disease appreciated alteration of immune regulation with predominance of the Th1 and Th17 phenotype cytokines. The profile of mucosal effector cytokines differs between refractory CD and active CD; however, maintain and worsen the inflammatory process. Immune dysregulation, loss of tolerance, increase of pro-inflammatory cytokines and non-suppression of the inflammatory response despite the presence of counter-regulatory mechanisms constitute relevant events in CD.

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Aberrant extrathymic T cell receptor gene rearrangement in the small intestinal mucosa: a risk factor for coeliac disease?

Cited by 9 publications

References 28 publications

Intestinal T-cell Responses in Celiac Disease – Impact of Celiac Disease Associated Bacteria

Intestinal T-cell Responses in Celiac Disease – Impact of Celiac Disease Associated Bacteria

Celiac disease

Celiac disease: Participation of Cytokines and Other Factors in the Immune Response

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