{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["10(4)"],"submitter":["Khilji MS"],"pubmed_abstract":["How immune tolerance is lost to pancreatic β-cell peptides triggering autoimmune type 1 diabetes is enigmatic. We have shown that loss of the proinsulin chaperone glucose-regulated protein (GRP) 94 from the endoplasmic reticulum (ER) leads to mishandling of proinsulin, ER stress, and activation of the immunoproteasome. We hypothesize that inadequate ER proinsulin folding capacity relative to biosynthetic need may lead to an altered β-cell major histocompatibility complex (MHC) class-I bound peptidome and inflammasome activation, sensitizing β-cells to immune attack. We used INS-1E cells with or without GRP94 knockout (KO), or in the presence or absence of GRP94 inhibitor PU-WS13 (GRP94i, 20 µM), or exposed to proinflammatory cytokines interleukin (IL)-1β or interferon gamma (IFNγ) (15 pg/m"],"journal":["Biomedicines"],"pagination":["814"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9024965"],"repository":["biostudies-literature"],"pubmed_title":["Defective Proinsulin Handling Modulates the MHC I Bound Peptidome and Activates the Inflammasome in β-Cells."],"pmcid":["PMC9024965"],"pubmed_authors":["Khilji MS","Purcell AW","Buus S","Mandrup-Poulsen T","Pandey K","Dahlby T","Faridi P","Klusek J","Pinheiro-Machado E","Marzec MT","Hoefner C","Nielsen M","Aranha R"],"additional_accession":[]},"is_claimable":false,"name":"Defective Proinsulin Handling Modulates the MHC I Bound Peptidome and Activates the Inflammasome in β-Cells.","description":"How immune tolerance is lost to pancreatic β-cell peptides triggering autoimmune type 1 diabetes is enigmatic. We have shown that loss of the proinsulin chaperone glucose-regulated protein (GRP) 94 from the endoplasmic reticulum (ER) leads to mishandling of proinsulin, ER stress, and activation of the immunoproteasome. We hypothesize that inadequate ER proinsulin folding capacity relative to biosynthetic need may lead to an altered β-cell major histocompatibility complex (MHC) class-I bound peptidome and inflammasome activation, sensitizing β-cells to immune attack. We used INS-1E cells with or without GRP94 knockout (KO), or in the presence or absence of GRP94 inhibitor PU-WS13 (GRP94i, 20 µM), or exposed to proinflammatory cytokines interleukin (IL)-1β or interferon gamma (IFNγ) (15 pg/m","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2025-04-22T21:41:50.623Z","creation":"2025-02-19T02:01:01.76Z"},"accession":"S-EPMC9024965","cross_references":{"pubmed":["35453564"],"doi":["10.3390/biomedicines10040814"]}}