Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline

Journals

Article Types

Countries / Regions

Search Results (1)

Search Parameters:
Keywords = autoreactive TCR transductants

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
16 pages, 37492 KB  
Article
Stem-Cell-Derived β-Like Cells with a Functional PTPN2 Knockout Display Increased Immunogenicity
by Taylor M. Triolo, J. Quinn Matuschek, Roberto Castro-Gutierrez, Ali H. Shilleh, Shane P. M. Williams, Maria S. Hansen, Kristen McDaniel, Jessie M. Barra, Aaron Michels and Holger A. Russ
Cells 2022, 11(23), 3845; https://doi.org/10.3390/cells11233845 - 30 Nov 2022
Cited by 4 | Viewed by 3530
Abstract
Type 1 diabetes is a polygenic disease that results in an autoimmune response directed against insulin-producing beta cells. PTPN2 is a known high-risk type 1 diabetes associated gene expressed in both immune- and pancreatic beta cells, but how genes affect the development of [...] Read more.
Type 1 diabetes is a polygenic disease that results in an autoimmune response directed against insulin-producing beta cells. PTPN2 is a known high-risk type 1 diabetes associated gene expressed in both immune- and pancreatic beta cells, but how genes affect the development of autoimmune diabetes is largely unknown. We employed CRISPR/Cas9 technology to generate a functional knockout of PTPN2 in human pluripotent stem cells (hPSC) followed by differentiating stem-cell-derived beta-like cells (sBC) and detailed phenotypical analyses. The differentiation efficiency of PTPN2 knockout (PTPN2 KO) sBC is comparable to wild-type (WT) control sBC. Global transcriptomics and protein assays revealed the increased expression of HLA Class I molecules in PTPN2 KO sBC at a steady state and upon exposure to proinflammatory culture conditions, indicating a potential for the increased immune recognition of human beta cells upon differential PTPN2 expression. sBC co-culture with autoreactive preproinsulin-reactive T cell transductants confirmed increased immune stimulations by PTPN2 KO sBC compared to WT sBC. Taken together, our results suggest that the dysregulation of PTPN2 expression in human beta cell may prime autoimmune T cell reactivity and thereby contribute to the development of type 1 diabetes. Full article
(This article belongs to the Collection Stem Cell Therapies for Treating Diabetes)
Show Figures

Figure 1

Back to TopTop