Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease and type I diabetes mellitus

Vorobjova, Tamara; Uibo, Oivi; Heilman, Kaire; Rägö, Tiina; Honkanen, Jarno; Vaarala, Outi; Tillmann, Vallo; Ojakivi, Ivi; Uibo, Raivo

doi:10.1080/00365520802624177

Cited by 54 publications

(51 citation statements)

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“…Transcription levels of the FoxP3 gene in the biopsy samples positively correlate to the number of CD4 1 CD25 1 FoxP3 1 regulatory T cells stained in the respective mucosal specimens, 14 whereas according to our experience with TJP1 immunocytochemical staining, differences between individuals with different TJP1 gene transcription levels in the intestinal mucosa are rather complicated to evaluate due to variable staining patterns on the same sample.…”

Section: Detection Of Serum Antibodiesmentioning

confidence: 83%

“…14 The transcription level of the TJP1 gene (Hs.510833) was evaluated using SYBR Green RT-PCR Gene Expression Analysis (SuperArray; Bioscience Corporation, Frederick, MD, USA). A total of 1 ml of cDNA from each sample was used for each duplicate measurement for human TJP1 (Hs.510833, SuperArray) in combination with 1 ml cDNA to measure the housekeeping gene b-actin (ACTB, Hs.…”

Section: Detection Of Serum Antibodiesmentioning

confidence: 99%

“…Studies have demonstrated that the number of CD4 1 CD25 1 FoxP3 1 regulatory T cells is increased in the small-bowel mucosa of CD patients; this increase might represent a compensatory mechanism to downregulate the elevated immune response to foreign and self-antigens. [13][14][15] Immune responses to the self-antigen tTG may be caused by the increased expression of tTG in the intestinal mucosa, 16 a conformational change in enzyme structure 17 or the release of intracellular tTG that, when picked up by dendritic cells, subsequently leads to the activation of adaptive immune responses. Antibodies against tTG may influence either the deamidating or the transamidating activity of the enzyme, which may lead to significant biological effects in intestine.…”

Section: Introductionmentioning

confidence: 99%

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Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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Two common chronic childhood diseases-celiac disease (CD) and type 1 diabetes (T1D)-result from complex pathological mechanisms where genetic susceptibility, environmental exposure, alterations in intestinal permeability and immune responses play central roles. In this study, we investigated whether these characteristics were universal for CD independently of T1D association. For this purpose, we studied 36 children with normal small-bowel mucosa and 26 children with active CD, including 12 patients with T1D. In samples from the small-bowel mucosa, we detected the lowest expression of tight junction protein 1 (TJP1) mRNA in CD patients with T1D, indicating an increase in intestinal permeability. Furthermore, these samples displayed the highest expression of forkhead box P3 (FoxP3) mRNA, a marker for regulatory T cells, as compared with other patient groups. At the same time, serum levels of IgA antibodies specific for the CD-related antigens deamidated gliadin and tissue transglutaminase (tTG) were the highest in CD patients with T1D. In contrast, no significant differences were found in IgA or IgG antibodies specific for bovine beta-lactoglobulin or Bifidobacterium adolescentis DSM 20083-derived proteins. There were also no differences in the transamidating activity of serum autoantibodies between patients and control individuals. Our results show that patients with T1D and newly detected CD exhibit severely altered intestinal permeability, strong local immune activation and increased immunoregulatory mechanisms in the small bowel. Further study is required to determine whether these extreme changes in this CD subgroup are due to some specific environmental factors (virus infections), unknown genetic effects or autoimmune reactions to antigenic targets in intracellular tight junctions. INTRODUCTIONWith an approximate prevalence of 1.0% in Western countries, celiac disease (CD) is one of the most common lifelong chronic disorders. 1 CD and type 1 diabetes (T1D) form a significant sector of childhood diseases with high rate of co-occurrence. 2 Both diseases are autoimmune in origin and develop as a result of complex pathological mechanisms, involving several common genetic, environmental and immunological factors. Among these, the common susceptibility loci of HLA and other immune system-related genes, 3 permeability changes in the small-bowel mucosa, 4 and association with wheat consumption 4,5 are prominent. Both diseases are increasing in most regions of the world, 6,7 as are several other autoimmune diseases, but the actual cause of the disease remains unknown. However, several recent studies have highlighted the role of environmental and social changes that have taken place over the last several decades. 8,9 The central event in the pathogenesis of CD is damage to the small intestinal mucosa that occurs after ingestion of gluten or related prolamins in genetically susceptible individuals. During this process, several morphological and immunological alterations have been demonstrated in the small-bowel mucos...

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Section: Detection Of Serum Antibodiesmentioning

confidence: 83%

Section: Detection Of Serum Antibodiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

et al. 2011

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“…+ FoxP3 + cells together with pronounced expression of FoxP3 mRNA have also been detected in small-bowel biopsy specimens from children diagnosed with both celiac disease and T1D [126,135] . Further, the density of FoxP3 + cells are also correlate with histological grade of atrophic changes in the small bowel [136] .…”

Section: T-regulatory Associated Immunitymentioning

confidence: 89%

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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“…These changes are accompanied by a gradual increase in the number of T cells and activation of immunoregulatory counteractions in the affected mucosa. 5,6 The damage to the intestinal mucosa in celiac sprue is due to an immunological reaction against gluten and related prolamines; there is also a very strong autoimmune component, in which tissue (or type 2) transglutaminase (tTG) has a central role. The mechanisms of autoimmunity development against tTG are not fully known, although several hypotheses have been proposed.…”

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confidence: 99%

Celiac disease: a model disease for gene–environment interaction

2011

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Increased FOXP3 expression in small-bowel mucosa of children with coeliac disease and type I diabetes mellitus

Cited by 54 publications

References 55 publications

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

Celiac disease in patients with type 1 diabetes: a condition with distinct changes in intestinal immunity?

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

Celiac disease: a model disease for gene–environment interaction

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