GSE155713: Modeling human T-cell mediated beta cell destruction

Gene Expression Data Explorer
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GROUP CONDITION SAMPLES
ES derived beta-like cells
GSM4711136 GSM4711137 GSM4711138 GSM4711139
GSM4711130 GSM4711131
H1-ES cells
GSM4711129
Human pancreatic islets
GSM4711132
GSM4711134
Pancreatic endocrine cells sorted from human pancreatic islets
GSM4711133
GSM4711135
Description

Submission Date: Aug 04, 2020

Summary: Autoimmune destruction of pancreatic β cells underlies type 1 diabetes (T1D). To understand T-cell mediated immune impact on human pancreatic β cells, we combine β cell specific expression of a model antigen CD19 and anti-CD19 chimeric antigen receptor T (CAR-T) cells. Co-culturing CD19-expressing -like cells and CD19 CAR-T cells results in T-cell mediated β-like cell death with release of activated T cell cytokines. Transcriptome analysis of β-like cells and human islets treated with conditioned medium of the immune reaction identifies upregulation of immune reaction genes and the pyroptosis mediator GSDMD as well as its activator CASP4. Caspase-4-mediated cleaved GSDMD is detected in β-like cells under inflammation and endoplasmic reticulum (ER) stress conditions. Among the immune regulatory genes, PDL1 is one of the most upregulated, and PDL1 overexpression partially protects β-like cells in mice transplanted with human β cells. This experimental platform identifies potential mechanisms of β cell destruction and may allow testing therapeutic strategies.

GEO Accession ID: GSE155713

PMID: 33205073

Description

Submission Date: Aug 04, 2020

Summary: Autoimmune destruction of pancreatic β cells underlies type 1 diabetes (T1D). To understand T-cell mediated immune impact on human pancreatic β cells, we combine β cell specific expression of a model antigen CD19 and anti-CD19 chimeric antigen receptor T (CAR-T) cells. Co-culturing CD19-expressing -like cells and CD19 CAR-T cells results in T-cell mediated β-like cell death with release of activated T cell cytokines. Transcriptome analysis of β-like cells and human islets treated with conditioned medium of the immune reaction identifies upregulation of immune reaction genes and the pyroptosis mediator GSDMD as well as its activator CASP4. Caspase-4-mediated cleaved GSDMD is detected in β-like cells under inflammation and endoplasmic reticulum (ER) stress conditions. Among the immune regulatory genes, PDL1 is one of the most upregulated, and PDL1 overexpression partially protects β-like cells in mice transplanted with human β cells. This experimental platform identifies potential mechanisms of β cell destruction and may allow testing therapeutic strategies.

GEO Accession ID: GSE155713

PMID: 33205073

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