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Gene expression profiling of Type II Enteropathy-associated T-cell lymphoma

ABSTRACT: Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8αα and CD8αβ T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters.

ORGANISM(S): Homo sapiens

PROVIDER: GSE70652 | GEO | 2016/03/03

SECONDARY ACCESSION(S): PRJNA289281

REPOSITORIES: GEO

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Gene expression profiling of Type II Enteropathy-associated T-cell lymphoma

Project description:Type II Enteropathy-associated T-cell lymphoma (Type II EATL) is an aggressive intestinal T-cell lymphoma with poor prognosis and has not been molecularly profiled. Through targeted amplicon sequencing, we identified a large portion of Type II EATL samples that harbor mutations in the STAT5B, JAK3 and GNAI2 genes. Here we performed gene expression profiling on four Type II EATL samples in order to better characterize this disease. As Type II EATL is suggested to arise from CD8+ IELs, we integrated our data with publicly available profile of CD8Î±Î± and CD8Î±Î² T-cells from healthy donors (GSE33374). Gene expression profiling independently demonstrated strong enrichment of several aspects of GPCR and JAK-STAT signaling pathways. Moreover, an significant association was identified with genes containing STAT5B binding sites in their promoters. Microarray gene expression profiling was performed on 4 Type II Enteropathy-associated T-cell lymphoma and a combination of unsupervised and supervised clustering was performed to determine any differentially activated pathways between samples with tumor and healthy human CD161++CD8aa and CD161++CD8ab T cells (found under accession number GSE33374)

2016-03-03 | E-GEOD-70652 | biostudies-arrayexpress

Affymetrix Genome-Wide Human SNP Array 6.0 data for Type II Enteropathy-associated T-cell lymphoma

2016-03-03 | GSE70653 | GEO

Affymetrix Genome-Wide Human SNP Array 6.0 data for Type II Enteropathy-associated T-cell lymphoma

2016-03-03 | E-GEOD-70653 | biostudies-arrayexpress

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

Transcriptome of RCD-2 biopsies

Project description:About 5% of celiac disease (CeD) patients do not respond to a gluten-free diet and progress to refractory celiac disease (RCD), a severe progression that is characterized by infiltration of intraepithelial T-lymphocytes (IELs). RCD type II (RCDII) patients show clonal expansions of IELs that result in a poor prognosis and a high mortality rate through development of aggressive enteropathy-associated T-cell lymphoma.<br>RCDII has a poor prognosis (5-year survival rate <50%) also because of the development of enteropathy-associated T-cell lymphoma. Diagnosis of RCDII is complex and involves a combination of several techniques such as multiplex PCR analysis to determine the clonality of T-cell receptor gene rearrangements and immunohistochemistry or flow-cytometry to define the cell surface markers of IELs. Therefore studying the genetics and genomics of RCD2 susceptibility may provide novel insights into mechanistic basis for RCD2 development. The aim of this experiment was to profile the global gene expression changes in order to understand the dysregulated pathways in RCD2 biopsies and to uncover downstream pathways affected by RCD2 genetic susceptibility loci. <br>All patients were diagnosed with RCD2 and gut biopsies were collected from these patients to perform microarray based gene expression analysis. RNA from eleven RCD2 biopsy samples were analyzed using Illumina Human Ref8 v1 array.

2016-12-05 | E-MTAB-4613 | biostudies-arrayexpress

BCL6 is required for the thymic development of TCRαβ+CD8αα+ intraepithelial lymphocyte lineage

Project description:TCRαβ+CD8αα+ intraepithelial lymphocytes (CD8αα+ αβ IELs), a specialized subset of T cells in the gut epithelium, develop from thymic agonist-selected IEL precursors (IELps). The molecular mechanisms underlying the selection and differentiation of this T cell type in the thymus are largely unknown. Here, we found that Bcl6 deficiency in αβ T cells resulted in nearly the absence of CD8αα+ αβ IELs. BCL6 was expressed by approximately 50% of CD8αα+ αβ IELs but the majority thymic PD1+ IELps post agonist selection; its deficiency blocked early IELp generation in the thymus. Moreover, BCL6 expression in IELps was induced by thymic TCR signaling in an ERK-dependent manner. As a result of Bcl6 deficiency, the precursors of IELps among CD4+CD8+ double positive (DP) thymocytes exhibited increased apoptosis during agonist selection, and impaired IELp differentiation and maturation. Taken together, our results elucidate BCL6 as a crucial transcription factor during the thymic development of CD8αα+ αβ IELs.

2024-02-26 | GSE248163 | GEO

Phenotypic and genomic analysis of an exceptional case of enteropathy associated T cell lymphoma

Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies. Comparative genomic hybridisation (CGH) analyses of an exceptional case of enteropathy associated T cell lymphoma

2010-06-17 | E-GEOD-17715 | biostudies-arrayexpress

Kdm6b is required for the maturation and function of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes

Project description:To under the role of Kdm6b in the regulation of intestinal TCRβ+CD8αα+ intraepithelial lymphocytes (IELs), Kdm6b was conditionally deleted in mouse T cells. Small intestinal TCRβ+CD8αα+ IELs were sorted by flow cytometry and RNA-seq was conducted to identify the differentially expressed genes.

2022-08-02 | GSE154444 | GEO

Genome-wide maps of chromatin state in mouse small intestinal intraepithelial lymphocytes.

Project description:We performed CUT&Tag-Seq against histone H3K27me3 in mouse small intestinal TCRβ+CD8αα+ intraepithelial lymphocytes (IELs) of wild-type mice to analyze epigenetic modifications.

2022-08-02 | GSE185798 | GEO

Comprehensive proteomics analyses of IL-15 driven activation of intestinal intraepithelial lymphocytes

Project description:Intestinal intraepithelial lymphocytes (IEL) are an abundant population of tissue-resident T cells that protect the gut from pathogens and maintain intestinal homeostasis. The cytokine IL-15 is trans-presented by epithelial cells to IEL in complex with the IL-15 receptor α chain (IL-15Rα) and plays essential roles both in maintaining IEL homeostasis, and in inducing IEL activation in response to epithelial stress. When overproduced, IL-15 is a key driver of the gluten-induced enteropathy Coeliac disease, through cytotoxic activation of IEL. To better understand how IL-15 directly regulates both homeostatic and inflammatory functions of IEL, we performed quantitative proteomics of IL-15/Rα-stimulated murine IEL, sorted into their 3 main subpopulations, TCRγδ CD8αα, TCRαβ CD8αβ and TCRαβ CD8αα expressing IEL. The data reveal that high IL-15/Rα stimulation licenses cell cycle activation, upregulates the biosynthetic machinery in IEL, increases mitochondrial respiratory capacity and induces expression of cell surface immune receptors and adhesion proteins that potentially drive IEL activation.

2021-05-10 | PXD025891 | Pride

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