Wheat Gluten Causes Dendritic Cell Maturation and Chemokine Secretion

Nikulina, Marina; Habich, Christiane; Flohé, Stefanie B.; Scott, Fraser W.; Kolb, Hubert

doi:10.4049/jimmunol.173.3.1925

Cited by 84 publications

(66 citation statements)

References 48 publications

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“…3). An environment loaded with wheat antigens could also promote the maturation of dendritic cells, as reported recently in wheat-treated dendritic cells from BALB/c mice [49].…”

Section: Discussionsupporting

confidence: 56%

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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Aims/hypothesis: Type 1 diabetes is the result of an inflammatory T helper 1 (Th1) lymphocyte-mediated beta cell destructive process. The majority of diabetesprone BioBreeding (BBdp) rats fed wheat protein-based diets, such as NTP-2000, develop type 1 diabetes and display a mild coeliac-like enteropathy. Mesenteric lymph nodes (MLNs), which drain the gut, are the major inductive site where dietary antigens are recognised in the gut-associated lymphoid tissue (GALT). We hypothesised that this compartment could be a site of abnormal wheat proteininduced Th1 cell activation. Methods: MLN cells were isolated from BBdp and BB control (BBc) rats that were fed NTP-2000 or a hydrolysed casein (HC)-based diet at ages that pre-date classic insulitis. The inflammatory status, phenotype and proliferation of these cells in response to wheat protein were determined. Results: The expression ratio of T-bet : Gata3, master transcription factors for Th1 and Th2 cytokines, was increased in the MLN from NTP-2000-fed BBdp rats compared with that from BBc rats, mainly due to decreased Gata3 expression. CD3 + CD4 + IFN-γ + T cells were more prevalent in the MLN of wheatfed BBdp rats, but remained at control levels in BBdp rats fed a diabetes-retardant HC diet. BBdp MLN cells proliferated in response to wheat protein antigens in a specific, dose-dependent manner, and >93% of cells were CD3 + CD4 + T cells. This proliferation was associated with a low proportion of CD4 + CD25 + T cells and a high proportion of dendritic cells in the MLN of BBdp rats. Conclusions/ interpretation: Before insulitis is established, the MLNs of wheat-fed BBdp rats contain an unusually high proportion of Th1 cells that proliferate specifically in response to wheat protein antigens.

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“…3). An environment loaded with wheat antigens could also promote the maturation of dendritic cells, as reported recently in wheat-treated dendritic cells from BALB/c mice [49].…”

Section: Discussionsupporting

confidence: 56%

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Chakir¹,

Lefebvre

Wang³

et al. 2005

Diabetologia

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“…47 Gliadin has been shown to be also a potent stimulus for macrophage proinflammatory gene expression and cytokine release. 48 Our recent data suggest that signaling of both functions is independent of TLR4 and TLR2 but is dependent on MyD88, a key adapter molecule in TLR/ interleukin-1 receptor signaling. 49 These data indicate that gliadin initiates intestinal permeability through the CXCR3-mediated, MyD88-dependent release of zonulin, 42,49 which enables paracellular translocation of gliadin and its subsequent interaction with macrophages within the intestinal submucosa ( Figure 5).…”

Section: Specific Autoimmune Diseases In Which Zonulin Involvement Hamentioning

confidence: 99%

Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

Fasano

2008

The American Journal of Pathology

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The anatomical and functional arrangement of the gastrointestinal tract suggests that this organ, beside its digestive and absorptive functions, regulates the trafficking of macromolecules between the environment and the host through a barrier mechanism. Under physiological circumstances, this trafficking is safeguarded by the competency of intercellular tight junctions, structures whose physiological modulation is mediated by, among others, the recently described protein zonulin. To prevent harm and minimize inflammation, the same paracellular pathway, in concert with the gut-associated lymphoid tissue and the neuroendocrine network, controls the equilibrium between tolerance and immunity to nonself antigens. The zonulin pathway has been exploited to deliver drugs, macromolecules, or vaccines that normally would not be absorbed through the gastrointestinal mucosal barrier. However, if the tightly regulated trafficking of macromolecules is jeopardized secondary to prolonged zonulin up-regulation, the excessive flow of nonself antigens in the intestinal submucosa can cause both intestinal and extraintestinal autoimmune disorders in genetically susceptible individuals. This new paradigm subverts traditional theories underlying the development of autoimmunity, which are based on molecular mimicry and/or the bystander effect, and suggests that the autoimmune process can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing intestinal barrier competency. Understanding the role of zonulin-dependent intestinal barrier dysfunction in the pathogenesis of autoimmune diseases is an area of translational research that encompasses many fields. The intestinal epithelium is the largest mucosal surface, providing an interface between the external environment and the mammalian host. Its exquisite anatomical and functional arrangements and the finely-tuned coordination of digestive, absorptive, motility, neuroendocrine, and immunological functions are testimonial of the complexity of the gastrointestinal (GI) system. Also pivotal is the regulation of molecular trafficking between the intestinal lumen and the submucosa via the paracellular space. The dimensions of the paracellular space are estimated to be between 10 and 15 Å, suggesting that under physiological circumstances, solutes with a molecular radius exceeding 15 Å (ϳ3.5 kDa) will be excluded from this uptake route. Macromolecule trafficking is dictated mainly by intestinal paracellular permeability, the regulation of which depends on the modulation of intercellular tight junctions (TJs). A century ago, TJs were conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. The contribution of the paracellular pathway of the GI tract to the general economy of molecule trafficking between environment and host, therefore, was judged to be negligible. It is now apparent that TJs are extremely dynamic structures involved in several key functions of the intestinal epithe...

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“…Polymyxin B is a LPS-binding antibiotic that has been widely used as LPS-neutralizing reagent to avoid the possible interference of LPS contaminations (34,35). After incubation with soluble DAP-PGN (50 ng) with polymyxin B (10 g) and then PO activity and melanin synthesis were examined (column 9).…”

Section: Dap-pgn Lys-pgn and ␤-13-glucan But Not Lps Activatementioning

confidence: 99%

A Synthetic Peptidoglycan Fragment as a Competitive Inhibitor of the Melanization Cascade

Park

Piao

et al. 2006

Journal of Biological Chemistry

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Wheat Gluten Causes Dendritic Cell Maturation and Chemokine Secretion

Cited by 84 publications

References 48 publications

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Wheat protein-induced proinflammatory T helper 1 bias in mesenteric lymph nodes of young diabetes-prone rats

Physiological, Pathological, and Therapeutic Implications of Zonulin-Mediated Intestinal Barrier Modulation

A Synthetic Peptidoglycan Fragment as a Competitive Inhibitor of the Melanization Cascade

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