Article

Adaptive and innate immune responses in celiac disease

University of Naples Federico II, Napoli, Campania, Italy
Immunology Letters (Impact Factor: 2.37). 08/2005; 99(2):141-5. DOI: 10.1016/j.imlet.2005.02.017
Source: PubMed

ABSTRACT Celiac disease (CD) is a complex small intestinal disorder due to a dysregulated immune response to wheat gliadin and related proteins which leads to a small intestinal enteropathy. It is generally accepted that CD is a T-cell mediated disease, in which, gliadin derived peptides, either in native form or deamidated by tissue transglutaminase, activate lamina propria infiltrating T lymphocytes which release proinflammatory cytokines. Recent studies indicate that gliadin contains also peptides able to activate an innate immune response. In particular, they induce a selective expansion of IEL, particularly TCRgamma/delta+ and CD8+TCR alpha/beta+ lymphocytes bearing the CD94 NK receptor, as well as a strong epithelial expression of MICA molecules which interact with NKG2D receptor expressed on TCRgamma/delta+ and NK cells. Most of the events of innate immune activation events are inhibited by antibodies neutralizing IL-15, thus confirming the key role of this cytokine as a mediator of intestinal mucosa damage induced by ingestion of gliadin. It remains to be established to what extent the ability of gliadin peptides to activate innate immunity relates to other biological properties exerted not only on celiac cells and tissues; the specificity of celiac patients is probably related to their genetic make up.

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    • "The main genetic influence on CD is the HLA locus [5], specifically MHC class II genes that encode HLA-DQ2 (HLA-DQ2.5 and HLA-DQ2.2) and HLA-DQ8 heterodimers. The prevalence of disease is usually reported to be about 1% in the general US population [6] but there "
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    ABSTRACT: Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. This is a complex disorder involving both environmental and immune-genetic factors. The major genetic risk factor for CD is determined by HLA-DQ genes. Dysfunction of the innate and adaptive immune systems can conceivably cause impairment of mucosal barrier function and development of localized or systemic inflammatory and autoimmune processes. Exposure to gluten is the main environmental trigger responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Thus, both genetic determination and environmental exposure to gluten are necessary for the full manifestation of CD; neither of them is sufficient alone. Epidemiological and clinical data suggest that other environmental factors, including infections, alterations in the intestinal microbiota composition, and early feeding practices, might also play a role in disease development. Thus, this interaction is the condicio sine qua non celiac disease can develop. The breakdown of the interaction among microbiota, innate immunity, and genetic and dietary factors leads to disruption of homeostasis and inflammation; and tissue damage occurs. Focusing attention on this interaction and its breakdown may allow a better understanding of the CD pathogenesis and lead to novel translational avenues for preventing and treating this widespread disease.
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    • "e l s e v i e r . c o m/ l o c a t e / j c s the adaptive system (Gianfrani et al., 2005). These peptides are generated in the gastrointestinal tract when gluten is partially proteolyzed by digestive enzymes. "
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    Journal of Cereal Science 01/2013; 59(1). DOI:10.1016/j.jcs.2013.10.006 · 1.94 Impact Factor
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    • "It is generally accepted that CD is a T-cell mediated disease, in which gliadin-derived peptides activate lamina propria, infiltrating T lymphocytes. This leads to the release of proinflammatory cytokines, such as IFN-γ and IL-15, which are responsible for the activation of the cytotoxicity of intraepithelial lymphocytes that leads to a profound tissue remodeling [1] [2]. This is a complex disorder, with environmental and genetic factors contributing to its etiology. "
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    ABSTRACT: Celiac disease (CD) is an immune-mediated enteropathy, triggered by dietary wheat gluten and similar proteins of barley and rye in genetically susceptible individuals. The etiology of this disorder is complex, involving both environmental and genetic factors. The major genetic risk factor for CD is represented by HLA-DQ genes, which account for approximately 40% of the genetic risk; however, only a small percentage of carriers develop the disease. Gluten is the main environmental factor responsible for the signs and symptoms of the disease, but exposure to gluten does not fully explain the manifestation of CD. Epidemiological and clinical data suggest that environmental factors other than gluten might play a role in disease development, including early feeding practices (e.g., breast milk versus formula and duration of breastfeeding), infections, and alterations in the intestinal microbiota composition. Herein, we review what is known about the influence of dietary factors, exposure to infectious agents, and intestinal microbiota composition, particularly in early life, on the risk of developing CD, as well as the possible dietary strategies to induce or increase gluten tolerance.
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