{"doi":"10.1111/imm.13594","title":"<scp>mTORC2</scp> contributes to systemic autoimmunity","abstract":"The development of many systemic autoimmune diseases, including systemic lupus erythematosus, is associated with overactivation of the type I interferon (IFN) pathway, lymphopenia and increased follicular helper T (Tfh)-cell differentiation. However, the cellular and molecular mechanisms underlying these immunological perturbations remain incompletely understood. Here, we show that the mechanistic target of rapamycin complex 2 (mTORC2) promotes Tfh differentiation and disrupts Treg homeostasis. Inactivation of mTORC2 in total T cells, but not in Tregs, greatly ameliorated the immunopathology in a systemic autoimmunity mouse model. This was associated with reduced Tfh differentiation, B-cell activation, and reduced T-cell glucose metabolism. Finally, we show that type I IFN can synergize with TCR ligation to activate mTORC2 in T cells, which partially contributes to T-cell lymphopenia. These data indicate that mTORC2 may act as downstream of type I IFN, TCR and costimulatory receptor ICOS, to promote glucose metabolism, Tfh differentiation, and T-cell lymphopenia, but not to suppress Treg function in systemic autoimmunity. Our results suggest that mTORC2 might be a rational target for systemic autoimmunity treatment.","journal":"Immunology","year":2022,"id":282816,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":959210,"name":"Haiyu Qi","orcid":null,"position":1,"is_corresponding":false},{"id":958841,"name":"Meilu Li","orcid":"0000-0003-3739-5643","position":2,"is_corresponding":false},{"id":580633,"name":"Yanfeng Li","orcid":"0000-0003-3446-4252","position":3,"is_corresponding":false},{"id":580632,"name":"Xingxing Zhu","orcid":"0000-0001-8411-319X","position":4,"is_corresponding":false},{"id":298878,"name":"Shreyasee Amin","orcid":"0000-0002-8940-2449","position":5,"is_corresponding":false},{"id":290231,"name":"Mariam P. Alexander","orcid":null,"position":6,"is_corresponding":false},{"id":957598,"name":"Catherine M.M. Diadhiou","orcid":"0000-0003-3389-5886","position":7,"is_corresponding":false},{"id":285335,"name":"Anne Davidson","orcid":"0000-0002-4081-6464","position":8,"is_corresponding":false},{"id":287643,"name":"Hu Zeng","orcid":"0000-0002-9909-7732","position":9,"is_corresponding":false},{"id":514460,"name":"Xian Zhou","orcid":"0000-0001-8766-8158","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T00:29:19.691592Z","pmid":"36273262","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}