Innate immunity is a late event in the onset of gliadin-specific enteropathy in the HLA-DQ8 mice.

Published on Jan 8, 2020in Immunobiology3.144
· DOI :10.1016/J.IMBIO.2020.151903
Francesco Maurano26
Estimated H-index: 26
(National Research Council),
Tasuku Ogita9
Estimated H-index: 9
(Shinshu University)
+ 5 AuthorsMauro Rossi63
Estimated H-index: 63
(National Research Council)
Sources
Abstract
Abstract Celiac disease (CD) is a food enteropathy that occurs in genetically susceptible individuals following the ingestion of gluten. Both gluten cytotoxicity and immunity activation play a role in CD pathogenesis; however, the chronological assessment of the different pathogenic mechanisms remains elusive. The models developed so far have only partially addressed this issue. Herein, Ab°DQ8 transgenic mice were administered wheat gliadin and indomethacin for 10 days to induce enteropathy. Gliadin-induced alteration of the small intestinal architecture was associated with increased expression of tissue transglutaminase in the lamina propria and a marked hypoxic environment. Enteropathic mice showed activation of innate immunity, featuring an increase of pro-inflammatory IFN-γ and IL-15 mRNAs, as well as CD11c+CD103+, CD11b+CD11c+, and CD11b+CD103+ dendritic cell subsets. However, the temporal assessment of examined parameters indicated that the induction of innate immunity during the generation of the mucosal lesion, occurred belatedly, highlighting a major role of gliadin intrinsic cytotoxicity in the pathogenic mechanism of this model. These results have important implications for the use of this model to test the impact of biotechnological interventions to reduce the cytotoxicity of gliadin.
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: Over the last ten years, immunologists have recognized the central importance of an emerging group of innate lymphoid cells (ILCs) in health and disease. Characterization of these cells has provided a molecular definition of ILCs and their tissue-specific functions. Although the lineage-defining transcription factors, cytokine production, and nomenclature parallel those of T helper cells, ILCs do not require adaptive immune programming. Both environmental and host-derived signals shape the fun...
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#1Merlin Nanayakkara (University of Naples Federico II)H-Index: 14
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Celiac disease (CD) is an autoimmune disease characterized by inflammation of the intestinal mucosa due to an immune response to wheat gliadins. Some gliadin peptides are resistant to intestinal digestion (e.g., A-gliadin P31–43) and induce a stress/innate immune response, but the reason why they are dangerous in the intestines of patients with CD is unknown. In the present study, P31–43 activated IFN-α, a mediator of the innate immune response in CD, in the intestine of subjects with CD and an ...
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#1Prashant Singh (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 63
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Background & Aims Celiac disease is a major public health problem worldwide. Although initially it was reported from countries with predominant Caucasian populations, it now has been reported from other parts of the world. The exact global prevalence of celiac disease is not known. We conducted a systematic review and meta-analysis to estimate the global prevalence of celiac disease. Methods We searched Medline, PubMed, and EMBASE for the keywords celiac disease, celiac, celiac disease, tissue t...
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#1Rodger Duffin (Medical Research Council)H-Index: 56
#2Richard A. O’Connor (Edin.: University of Edinburgh)H-Index: 10
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Systemic inflammation, which results from the massive release of proinflammatory molecules into the circulatory system, is a major risk factor for severe illness, but the precise mechanisms underlying its control are not fully understood. We observed that prostaglandin E2 (PGE2), through its receptor EP4, is down-regulated in human systemic inflammatory disease. Mice with reduced PGE2 synthesis develop systemic inflammation, associated with translocation of gut bacteria, which can be prevented b...
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#1Giuseppe Mazzarella (National Research Council)H-Index: 31
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Celiac disease (CD) is an enteropathy caused by the ingestion of wheat gluten in genetically susceptible individuals. A complete understanding of the pathogenic mechanisms in CD has been hindered because of the lack of adequate in vivo models. In the present study, we explored the events after the intragastric administration of gliadin and of the albumin/globulin fraction from wheat in human leukocyte antigen-DQ8 transgenic mice (DQ8 mice) treated with indomethacin, an inhibitor of cyclooxygenas...
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#1Valérie Abadie (UdeM: Université de Montréal)H-Index: 17
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Abstract Background Celiac disease (CD) is an immune-mediated disorder caused by the ingestion of wheat gluten. A lifelong, gluten-free diet is required to normalize the intestinal mucosa. We previously found that transamidation by microbial transglutaminase (mTGase) suppressed the gliadin-specific immune response in intestinal T-cell lines from CD patients and in models of gluten sensitivity. Methods SDS-PAGE, Western blot, ELISA, tissue transglutaminase (tTGase) assay and nano-HPLC–ESI-MS/MS e...
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#1Emma Persson (Lund University)H-Index: 25
#2Heli Uronen-Hansson (Lund University)H-Index: 16
Last. William W. Agace (UCPH: University of Copenhagen)H-Index: 61
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Summary CD103 + CD11b + dendritic cells (DCs) represent the major migratory DC population within the small intestinal lamina propria (SI-LP), but their in vivo function remains unclear. Here we demonstrate that intestinal CD103 + CD11b + DC survival was dependent on interferon regulatory factor 4 (IRF4). Mice with a DC deletion in Irf4 displayed reduced numbers of intestinal interleukin 17 (IL-17)-secreting helper T 17 (Th17) cells and failed to support Th17 cell differentiation in draining mese...
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#1You Yi Hwang (LMB: Laboratory of Molecular Biology)H-Index: 5
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The family of innate lymphoid cells (ILCs) comprises of natural killer (NK) cells, Rorγt-dependent ILCs (lymphoid tissue inducer (LTi) cells, ILC22, and ILC17), and type 2 ILCs. Apart from a common requirement for inhibitor of DNA binding 2 (Id2) expression and common γ-chain (γc) signaling, the differentiation of ILC populations is regulated by distinct transcription factors. ILCs play fundamental roles in processes such as cytotoxicity, lymphoid organogenesis, intestinal homeostasis, immunity ...
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#1Mariela Bayardo (UNLP: National University of La Plata)H-Index: 4
Transglutaminase 2 (TG2) is expressed ubiquitously, has multiple physiological functions and has also been associated with inflammatory diseases, neurodegenerative disorders, autoimmunity and cancer. In particular, TG2 is expressed in small intestine mucosa where it is up-regulated in active coeliac disease (CD). The aim of this work was to investigate the induction of TG2 expression by proinflammatory cytokines [interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, interferon (IFN)-γ and IL...
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Various types of transgenic mice carrying either class I or II human leukocyte antigen (HLA) molecules are readily available, and reports describing their use in a variety of studies have been publ...
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