{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["He Q"],"funding":["National Natural Science Foundation of China","the Postgraduate Innovative Research Program of Jiangsu Province"],"pagination":["1102-1116"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9508111"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["19(10)"],"pubmed_abstract":["The specification of the αβ/γδ lineage and the maturation of medullary thymic epithelial cells (mTECs) coordinate central tolerance to self-antigens. However, the mechanisms underlying this biological process remain poorly clarified. Here, we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation, promoted thymic IL-17A-producing γδ T-cell (Tγδ17) lineage commitment, and led to the development of fatal autoimmune hepatitis (AIH) via different mechanisms. Transfer of γδ T cells from TOX-deficient mice reproduced AIH. TOX interacted with and stabilized the TCF1 protein to maintain the balance of γδ T-cell development in thymic progenitors, and overexpression of TCF1 normalized αβ/γδ lineage specification and activation. In addition, TOX expression was downre"],"journal":["Cellular & molecular immunology"],"pubmed_title":["TOX deficiency facilitates the differentiation of IL-17A-producing γδ T cells to drive autoimmune hepatitis."],"pmcid":["PMC9508111"],"funding_grant_id":["82120108012 to BS"],"pubmed_authors":["Liu Y","Sun M","Tian W","Wu N","Lu Y","Sun B","Zhang H","Dong Z","Jiang R","Yu W","Wang F","He Q"],"additional_accession":[]},"is_claimable":false,"name":"TOX deficiency facilitates the differentiation of IL-17A-producing γδ T cells to drive autoimmune hepatitis.","description":"The specification of the αβ/γδ lineage and the maturation of medullary thymic epithelial cells (mTECs) coordinate central tolerance to self-antigens. However, the mechanisms underlying this biological process remain poorly clarified. Here, we report that dual-stage loss of TOX in thymocytes hierarchically impaired mTEC maturation, promoted thymic IL-17A-producing γδ T-cell (Tγδ17) lineage commitment, and led to the development of fatal autoimmune hepatitis (AIH) via different mechanisms. Transfer of γδ T cells from TOX-deficient mice reproduced AIH. TOX interacted with and stabilized the TCF1 protein to maintain the balance of γδ T-cell development in thymic progenitors, and overexpression of TCF1 normalized αβ/γδ lineage specification and activation. In addition, TOX expression was downre","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-05-28T02:02:21.161Z","creation":"2025-04-05T15:24:37.234Z"},"accession":"S-EPMC9508111","cross_references":{"pubmed":["35986136"],"doi":["10.1038/s41423-022-00912-y"]}}