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Gene expression assessed by genome wide hybridization bead array in intraepithelial lymphocytes (IELs) isolated from small intestinal biopsies of celiac disease patients with active disease and clinical controls

ABSTRACT: Analysis of role of small intestinal intraepithelial lymphocytes (IELs) in the immunopathology of celiac disease

ORGANISM(S): Homo sapiens

PROVIDER: GSE102993 | GEO | 2017/08/24

SECONDARY ACCESSION(S): PRJNA399708

REPOSITORIES: GEO

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INTERLEUKIN 15-DEPENDENT T CELL-LIKE INNATE INTRAEPITHELIAL LYMPHOCYTES DEVELOP IN THE INTESTINE AND TRANSFORM INTO LYMPHOMAS IN CELIAC DISEASE

Project description:The nature of gut intraepithelial lymphocytes lacking antigen receptors remains controversial. Herein we showed that, in humans and in mice, innate intestinal intraepithelial lymphocytes expressing intracellular CD3 (iCD3+ innate IELs) differentiate along an Id2 transcription factor (TF)-independent pathway in response to TF NOTCH1, interleukin 15 (IL-15) and Granzyme B signals. In NOTCH1-activated human hematopoietic precursors, IL-15 induced Granzyme B, which cleaved NOTCH1 into a peptide lacking transcriptional activity. As a result, NOTCH1 target genes indispensable for T cell differentiation were silenced and precursors were reprogrammed into innate cells with T cell marks including intracellular CD3 and T cell rearrangements. This pathway was operational in vivo in the mouse gut and led to the local differentiation of iCD3+ innate IELs from a bone marrow-derived precursor. In a subset of celiac patients, iCD3+ innate IELs with gain-of-function mutations in Janus kinase 1 or Signal transducer and activator of transcription 3 displayed enhanced response to IL-15 and acquired a selective advantage that favored clonal expansion and transformation into lymphoma. Overall we characterized gut T cell-like innate IELs, deciphered their pathway of differentiation, and showed their malignant transformation in celiac disease.

2016-11-23 | E-MTAB-4960 | biostudies-arrayexpress

Gene expression assessed by genome wide hybridization bead array in intestinal epithelial cells (IECs) isolated from small intestinal biopsies of celiac disease patients with active disease and clinical controls

Project description:Analysis of role of small intestinal epithelial cells (IECs) in the immunopathology of celiac disease

2017-08-24 | GSE102991 | GEO

Gluten induces rapid reprogramming of natural memory αβ and γδ intraepithelial T cells to induce cytotoxicity in celiac disease

Project description:Celiac disease (CD) is an autoimmune disease in which intestinal inflammation is induced by dietary gluten. The means through which gluten-specific CD4+T cell activation culminates in intraepithelial T cell (T-IEL)–mediated intestinal damage remain unclear. Here, we performed multiplexed single-cell analysis of intestinal and gluten-induced peripheral blood T cells from patients in different CD states and healthy controls. Untreated, active, and potential CD were associated with an enrichment of activated intestinal T cell populations, including CD4+follicular T helper (TFH) cells, regulatory T cells (Tregs), and natural CD8+αβ and γδ T-IELs. Natural CD8+αβ and γδ T-IELs expressing activating natural killer cell receptors (NKRs) exhibited a distinct TCR repertoire in CD and persisted in patients on a gluten-free diet without intestinal inflammation. Our data further show that NKR-expressing cytotoxic cells, which appear to mediate intestinal damage in CD, arise from a distinct NKR-expressing memory population of T-IELs. After gluten ingestion, both αβ and γδ T cell clones from this memory population of T-IELs circulated systemically along with gluten-specific CD4+T cells and assumed a cytotoxic and activating NKR-expressing phenotype. Collectively, these findings suggest that cytotoxic T cells in CD are rapidly mobilized in parallel with gluten-specific CD4+T cells after gluten ingestion.

2024-01-13 | GSE252762 | GEO

Reprogramming of CTLs into natural killer-like cells in celiac disease

Project description:Celiac disease is an intestinal inflammatory disorder induced by dietary gluten in genetically susceptible individuals. The mechanisms underlying the massive expansion of interferon g–producing intraepithelial cytotoxic T lymphocytes (CTLs) and the destruction of the epithelial cells lining the small intestine of celiac patients have remained elusive. We report massive oligoclonal expansions of intraepithelial CTLs that exhibit a profound genetic reprogramming of natural killer (NK) functions. These CTLs aberrantly expressed cytolytic NK lineage receptors, such as NKG2C, NKp44, and NKp46, which associate with adaptor molecules bearing immunoreceptor tyrosine-based activation motifs and induce ZAP-70 phosphorylation, cytokine secretion, and proliferation independently of T cell receptor signaling. This NK transformation of CTLs may underlie both the self-perpetuating, gluten-independent tissue damage and the uncontrolled CTL expansion leading to malignant lymphomas in severe forms of celiac disease. Because similar changes were detected in a subset of CTLs from cytomegalovirus-seropositive patients, we suggest that a stepwise transformation of CTLs into NK-like cells may underlie immunopathology in various chronic infectious and inflammatory diseases. Keywords: NKG2C; LAK; CTL; NK receptor; IEL; Mucosal Immunity; Celiac Disease

2006-05-15 | GSE4592 | GEO

Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease

Project description:Chronic inflammation driven by persistent antigenic challenge with dietary gluten permanently reshapes the tissue-resident TCRgd+ intraepithelial lymphocyte compartment in patients with celiac disease.

2018-12-12 | GSE123649 | GEO

Gene expression assessed by genome wide hybridization bead array in T84 polarized tight monolayers after challenge with celiac disease-associated bacteria [CTR 22 28 27]

Project description:Analysis of the influence of celiac disease-associated bacteria on intestinal epithelial cells

2017-08-26 | GSE103107 | GEO

Gene expression assessed by genome wide hybridization bead array in T84 polarized tight monolayers after challenge with celiac disease-associated bacteria [CTR 32 33 34]

Project description:Analysis of the influence of celiac disease-associated bacteria on intestinal epithelial cells

2017-09-20 | GSE103992 | GEO

Gene expression signatures for CD8αβ+ intraepithelial lymphocytes and CD8αβ+ splenocytes.

Project description:CD8αβ+ intraepithelial lymphocytes (IELs) are a subset of “effector-memory-like” T cells scattered along the intestinal epithelium. To investigate if CD8αβ+ IEL can function in ways other than the conventional cytotoxic effect of CD8αβ+ T cells,CD8αβ+ IELs were compared with CD8αβ+ splenocytes (SPL) by RNA-seq. We used microarrays to identify new functions of CD8αβ+ IELs .

2018-05-30 | GSE105061 | GEO

RNA sequencing derived from intestinal biopsies from healthy controls and celiac disease patients

Project description:Aim: To compare the overall transcriptional profile in healthy controls and celiac disease patients. This dataset, was used to evaluate if our in vitro model (intestinal intraepithelial lymphocytes, desccribed in doi:10.1016/j.jaut.2020.10242 ) is representative of the transcriptional profile in the intestine under healthy or inflammatory conditions. Samples: Upper colonoscopy biopsies from 5 control and 11 celiac disease patients were taken, total RNA was extracted and RNA-sequencing was performed (without replicates)

2021-02-16 | GSE146190 | GEO

Examining the role of murine norovirus (MNV)-infection on intraepithelial lymphocytes (IELs).

Project description:We examined how MNV-infection affects the population and function of IELs in vivo.

2022-07-01 | GSE204822 | GEO