{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["134(23)"],"submitter":["Cattin-Roy AN"],"pubmed_abstract":["Type 1 diabetes (T1D) develops spontaneously despite functional antigen presentation machinery in the thymus and a perceptible central tolerance process. We found that intrathymic enrichment with IL-4 fine tunes signaling through the IL-4/IL-13 heteroreceptor (HR) in early thymic progenitors (ETPs), augments negative selection of self-reactive T cells, sustains a diverse T cell repertoire devoid of clones expressing disease-associated T cell receptor (TCR) genes, and protects the nonobese diabetic (NOD) mouse from T1D. Indeed, optimal IL-4 activates STAT transcription factors to program ETP fate decision toward CD11c+CD8α+ dendritic cells (DCs) agile in negative T cell selection and clonal deletion of diabetogenic T cells. However, due to diminished invariant natural killer T (iNKT) 2 cell frequency in the NOD thymus, IL-4 is as suboptimal level, metering STAT activation to program ETP fate decision toward the T cell lineage leading to diminished negative selection, a clonally restricted TCR repertoire, and manifestation of spontaneous T1D. These insights uncover yet another interplay by which IL-4 affects T1D."],"journal":["The Journal of clinical investigation"],"pagination":["e163417"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11601892"],"repository":["biostudies-literature"],"pubmed_title":["Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice."],"pmcid":["PMC11601892"],"pubmed_authors":["Laffey KG","Le LB","Schrum AG","Zaghouani H","Cattin-Roy AN"],"additional_accession":[]},"is_claimable":false,"name":"Reduced thymic IL-4 impairs negative T cell selection in nonobese diabetic mice.","description":"Type 1 diabetes (T1D) develops spontaneously despite functional antigen presentation machinery in the thymus and a perceptible central tolerance process. We found that intrathymic enrichment with IL-4 fine tunes signaling through the IL-4/IL-13 heteroreceptor (HR) in early thymic progenitors (ETPs), augments negative selection of self-reactive T cells, sustains a diverse T cell repertoire devoid of clones expressing disease-associated T cell receptor (TCR) genes, and protects the nonobese diabetic (NOD) mouse from T1D. Indeed, optimal IL-4 activates STAT transcription factors to program ETP fate decision toward CD11c+CD8α+ dendritic cells (DCs) agile in negative T cell selection and clonal deletion of diabetogenic T cells. However, due to diminished invariant natural killer T (iNKT) 2 cell frequency in the NOD thymus, IL-4 is as suboptimal level, metering STAT activation to program ETP fate decision toward the T cell lineage leading to diminished negative selection, a clonally restricted TCR repertoire, and manifestation of spontaneous T1D. These insights uncover yet another interplay by which IL-4 affects T1D.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2025-04-04T00:21:51.725Z","creation":"2025-04-04T00:21:51.725Z"},"accession":"S-EPMC11601892","cross_references":{"pubmed":["39621313"],"doi":["10.1172/JCI163417"]}}