IL-15 Interferes With Suppressive Activity of Intestinal Regulatory T Cells Expanded in Celiac Disease

Zanzi, Delia; Stefanile, Rosita; Santagata, Sara; Iaffaldano, Laura; Iaquinto, Gaetano; Giardullo, Nicola; Lania, Giuliana; Vigliano, Ilaria; Vera, Aufiero Rotondi; Ferrara, Katia; Auricchio, Salvatore; Troncone, Riccardo; Mazzarella, Giuseppe

doi:10.1038/ajg.2011.80

Cited by 97 publications

(101 citation statements)

References 28 publications

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“…In our experience, potential CD patients account for about 12% of children who undergo a small intestinal biopsy for suspected CD, and most of them remain healthy aft er 9 years of follow-up ( 27 ). In other words, they lack the fi nal destructive phase of CD.…”

Section: Discussionmentioning

confidence: 99%

In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease

Borrelli¹,

Gianfrani

Lania³

et al. 2016

American Journal of Gastroenterology

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Section: Discussionmentioning

confidence: 99%

In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease

Borrelli¹,

Gianfrani

Lania³

et al. 2016

American Journal of Gastroenterology

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“…Surprisingly, expression of FoxP3 was found to be reduced in patients with NCGS compared to CD, perhaps in the context of a generally reduced activation of adaptive immunity in NCGS relative to CD patients [63]. However, the overall expression of this and other messengers (e.g., TGF-β1, and IL-10) represents a rather controversial aspect of CD autoimmunity, because both downregulation and upregulation of FoxP3 and other T reg -dependent molecules have been reported in patients with CD and related autoimmune conditions (e.g., type 1 diabetes mellitus) [72][73][74][75][76].…”

Section: Non-celiac Gluten Sensitivitymentioning

confidence: 99%

Non-Celiac Gluten Sensitivity: Literature Review

Mansueto

Seidita

D’Alcamo

et al. 2014

Journal of the American College of Nutrition

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Key words: non-celiac gluten sensitivity, celiac disease, wheat allergy, food allergy, HLA, flow cytometric basophil activation test, innate immune response Background: A significant percentage of the general population report problems caused by wheat and/or gluten ingestion, even though they do not have celiac disease (CD) or wheat allergy (WA), because they test negative both for CD-specific serology and histopathology and for immunoglobulin E (IgE)-mediated assays. Most patients report both gastrointestinal and nongastrointestinal symptoms, and all report improvement of symptoms on a gluten-free diet. This clinical condition has been named non-celiac gluten sensitivity (NCGS).Aim: We attempt to define the current pathogenic, clinical, and diagnostic criteria of this "new" disease, to provide a practical view that might be useful to evaluate, diagnose, and manage NCGS patients.Methods: We reviewed the international literature through PubMed and Medline, using the search terms "wheat (hyper)sensitivity," "wheat allergy," "wheat intolerance," "gluten (hyper)sensitivity," and "gluten intolerance," and we discuss current knowledge about NCGS.Results: It has been demonstrated that patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course. NCGS diagnosis can be reached only by excluding CD and WA. Recent evidence shows that a personal history of food allergy in infancy, coexistent atopy, positive for immunoglobulin G (IgG) antigliadin antibodies and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.Conclusions: Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroups. Key teaching points:• Most patients report both gastrointestinal and nongastrointestinal symptoms, and all agree that there is an improvement of symptoms on a gluten-free diet.• NCGS diagnosis can be reached only by excluding celiac disease and wheat allergy.• Patients suffering from NCGS are a heterogeneous group, composed of several subgroups, each characterized by different pathogenesis, clinical history, and, probably, clinical course.• A personal history of food allergy in infancy, coexistent atopy, positive IgG antigliadin antibodies (AGA) and flow cytometric basophil activation test, with wheat and duodenal and/or ileum-colon intraepithelial and lamina propria eosinophil counts, could be useful to identify NCGS patients.• Future research should aim to identify reliable biomarkers for NCGS diagnosis and to better define the different NCGS subgroup. Abbreviations: CD = celiac disease, WA = wheat allergy, NCGS = non-celiac gluten sensitivity, GFD = gluten-free diet, IBS = irritable bowel syndrome, HLA = human leukocyte antigen, tTg = antitissue transglutaminase, AGA = antigliadin antibodies, EMA = endomysial antigen, DGP = deami...

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Section: Celiac Diseasementioning

confidence: 99%

“…In duodenal biopsy samples from patients with an active celiac disease a higher density of CD4 + CD25 + FoxP3 + T cells has been observed in comparison to patients with treated celiac disease and healthy controls [97] . In co-culture, these Treg cells are shown to be functionally suppressive, but their activity is impaired by for example IL-15 [97] . Contrary, a low grade inflammation has been detected in individuals with potential risk of developing celiac disease who still have a normal small intestinal mucosa but with a positive CD-associated serology [98] .…”

Section: Celiac Diseasementioning

confidence: 99%

Children diagnosed with both Type 1 diabetes and Celiac disease - An Immunological challenge

Faresjö

2016

Immunoendocrinology

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Type 1 diabetes (T1D) and celiac disease are both characterized by an autoimmune feature. As T1D and celiac disease share several common risk factors such as environment, genetics and immune dysregulation, patients have risk of developing the other disease subsequently. Patients with manifest T1D may have had a latent celiac disease, which is activated parallel to the anti-islet immune reactivity during the development of T1D. Contrary, a low prevalence of β-cell autoimmunity is found in young patients with celiac disease. The role of antigen-specific T cells and their relation to cytokines and chemokines is not well characterized in children with combination of T1D and celiac disease. Defective regulation and an impaired ability of responder T cells to be suppressed are suggested to contribute. We have previously shown that children suffering from these two immunological diseases in combination have a suppressed immune response to several antigens for example food antigens like gluten. Poor development of oral tolerance seen as immune aberrancies with low percentages of both early and late effector memory CD8 + cells in the gut of children who are prone to T1D may predispose for development of celiac disease. This review highlights the immunological complexity in these two common pediatric immunological disorders that indicates that the combination of type 1 diabetes and celiac disease is an immunological challenge. It is obvious that we are far from understanding the immunological impact of these two autoimmune diseases in combination. This immunological challenge therefore needs to be elucidated to be able to predict and prevent these autoimmune diseases.

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IL-15 Interferes With Suppressive Activity of Intestinal Regulatory T Cells Expanded in Celiac Disease

Abstract: These data suggest that CD4+CD25+Foxp3+ T cells are induced in situ by gliadin. However, their suppressor capacity might be impaired in vivo by IL-15; this phenomenon contributes to maintain and expand the local inflammatory response in CD.

Cited by 97 publications

References 28 publications

In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease

In the Intestinal Mucosa of Children With Potential Celiac Disease IL-21 and IL-17A are Less Expressed than in the Active Disease

Non-Celiac Gluten Sensitivity: Literature Review

Children diagnosed with both Type 1 diabetes and Celiac disease - An Immunological challenge

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