Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria.

Tagliabue, Aldo; Befus, A D; Clark, David A.; Bienenstock, John

doi:10.1084/jem.155.6.1785

Cited by 202 publications

(86 citation statements)

References 27 publications

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“…Zonulin, which can induce tight junction disassembly and increase intestinal permeability, is upregulated in T1D, and gliadin induces zonulin upregulation in the intestinal cell line Caco2 [37]. This may result in direct stimulation of NK cells present in the lamina propia by gliadin or APCs [38,39]. It has also been suggested that gluten peptides might be presented by DCs sampling the intestinal lumen [40], which may increase the crosstalking with NK cells [14], thus making it possible for gliadin to activate NK cells even in the absence of a leaky gut epithelium.…”

Section: Discussionmentioning

confidence: 99%

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

et al. 2014

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Dietary gluten influences the development of type 1 diabetes in nonobese diabetic (NOD) mice and biobreeding rats, and has been shown to influence a wide range of immunological factors in the pancreas and gut. In the present study, the effects of gluten on NK cells were studied in vitro and in vivo. We demonstrated that gliadin increased direct cytotoxicity and IFN-γ secretion from murine splenocytes and NK cells toward the pancreatic beta-cell line MIN6 cells. Additionally, stimulation of MIN6 cells led to a significantly increased proportion of degranulating C57BL/6 CD107a + NK cells. Stimulation of C57BL/6 pancreatic islets with gliadin significantly increased secretion of IL-6 more than ninefold. In vivo, the gluten-containing diet led to a higher expression of NKG2D and CD71 on NKp46 + cells in all lymphoid organs in BALB/c and NOD mice compared with the gluten-free diet. Collectively, our data suggest that dietary gluten increases murine NK-cell activity against pancreatic beta cells. This mechanism may contribute to development of type 1 diabetes and explain the higher disease incidence associated with gluten intake in NOD mice.Keywords: C56BL/6 mice r Gliadin r Gluten r NK cells r NOD mice r Type 1 diabetes Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionDietary gluten is the initiating factor in the development of celiac disease (CD), however, an association between CD and type 1 diabetes (T1D) has been established. A gluten-free (GF) diet has been shown to have a protective effect against the development of T1D. It has been demonstrated that a GF diet in nonobese diabetic (NOD) mice reduces diabetes incidence from 64 to 15% [1], and similar results have been obtained with biobreeding rats [2]. Increased intestinal permeability occurs prior to the onset of T1D in both spontaneous animal models and human disease [3,4]. Patients with both CD and T1D diseases carry high-risk HLA alleles [5], and approximately 10% of T1D patients have anCorrespondence: Jesper Larsen e-mail: jelars@gmail.com increased prevalence of CD [6]. Moreover, T1D rarely develops after diagnosed CD, which may be because of the protective effect of a GF diet [7]. A recently published case report describes a boy with T1D who was able to maintain a low fasting blood glucose level without insulin therapy for more than 20 months after the time of diagnosis by adhering to a GF diet [8]. Lately, it has also been suggested that a family of gluten proteins known as gliadins may contribute directly to beta-cell hyperactivity, as enzymatically digested gliadin and a 33-mer gliadin fragment increase insulin secretion from beta cells by affecting the K ATP channel current [9]. This process could induce increased Ag expression of the beta-cell surface and prevent beta-cell rest [10]. Gliadin has been shown to stimulate several components of the adaptive immune system, such as Treg cells, Th17 cells, and DCs [11,12]. Gliadin fragments have also been shown to stimulate TLR4 a...

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Section: Discussionmentioning

confidence: 99%

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

et al. 2014

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“…NK cells are found in the murine intestinal epithelium and in the lamina propria (5,6) and NK T cells in the gut (7). Intestinal NK cells have cytotoxic (5) and IFN-␥ production activity (6).…”

Section: Eliac Disease (Cd)mentioning

confidence: 99%

“…Intestinal NK cells have cytotoxic (5) and IFN-␥ production activity (6). The expansion of intraepithelial lymphocytes expressing CD94, a typical NK cell receptor (8), and of a subset of gut epithelium CD3 Ϫ CD56 ϩ lymphocytes (9) has been described in CD.…”

Section: Eliac Disease (Cd)mentioning

confidence: 99%

Gliadin Regulates the NK-Dendritic Cell Cross-Talk by HLA-E Surface Stabilization

Terrazzano

Sica

Gianfrani

et al. 2007

The Journal of Immunology

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We analyzed the autologous NK cell interaction with gliadin-presenting dendritic cells. Gliadin is the known Ag priming the celiac disease (CD) pathogenesis. We demonstrate that gliadin prevents immature dendritic cells (iDCs) elimination by NK cells. Furthermore, cooperation between human NK cells-iDCs and T cells increases IFN-γ production of anti-gliadin immune response. Gliadin fractions were analyzed for their capability to stabilize HLA-E molecules. The α and ω fractions conferred the protection from NK cell lysis to iDCs and increased their HLA-E expression. Gliadin pancreatic enzyme digest and a peptide derived from gliadin α increased HLA-E levels on murine RMA-S/HLA-E-transfected cells. Analysis of HLA-E expression in the small intestinal mucosa of gluten-containing diet celiac patients and organ culture experiments confirmed the in vitro data.

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“…Lymphocytes from perfused liver were obtained according to the method described by Goossens et al (48). Intraepithelial lymphocytes (IELs) were prepared and purified through discontinuous 40%/70% Percoll gradient centrifugation as described by Tagliabue et al (49). Thymic stromal cell suspensions were prepared by digesting thymic lobes in 0.1% trypsin and 0.5 mM EDTA for 40 min at 37 o C. Digestion was stopped by addition of immunofluorescence (IF) buffer (HBSS containing 2% FBS and 0.1% NaN 3 ).…”

Section: Cell Preparation and Flow Cytometrymentioning

confidence: 99%

Expression of CD1d Under the Control of a MHC Class Ia Promoter Skews the Development of NKT Cells, But Not CD8+ T Cells

Chun

Colmone

et al. 2003

The Journal of Immunology

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Although CD1d and MHC class Ia share similar overall structure, they have distinct levels and patterns of surface expression. While the expression of CD1d1 is known to be essential for the development of NKT cells, the contribution of CD1d1 to the development of CD8+ T cells appears to be inconsequential. To investigate whether CD1d tissue distribution and expression levels confer differential capacity in selecting these two T cell subsets, we analyzed CD8 and NKT cell compartments in Kb-CD1d-transgenic mice that lack endogenous MHC class Ia and CD1d, respectively. We found that MHC class Ia-like expression pattern and tissue distribution are not sufficient for CD1d to rescue the development of CD8+ T cells, suggesting that unique structural features of CD1d preclude its active participation in selection of CD8+ T cells. Conversely, cell type-specific CD1d surface density is important for the selection of NKT cells, as the NKT cell compartment was only partially rescued by the Kb-CD1d transgene. We have previously demonstrated that increased CD1d expression on dendritic cells enhanced negative selection of NKT cells. In this study, we show that cell type-specific expression levels of CD1d establish a narrow window between positive and negative selection, suggesting that the distinct CD1d expression pattern may be selected evolutionarily to ensure optimal output of NKT cells.

show abstract

Characteristics of natural killer cells in the murine intestinal epithelium and lamina propria.

Cited by 202 publications

References 27 publications

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

Dietary gluten increases natural killer cell cytotoxicity and cytokine secretion

Gliadin Regulates the NK-Dendritic Cell Cross-Talk by HLA-E Surface Stabilization

Expression of CD1d Under the Control of a MHC Class Ia Promoter Skews the Development of NKT Cells, But Not CD8+ T Cells

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