{"doi":"10.1038/s41590-022-01372-2","title":"The phosphatidylinositol-transfer protein Nir3 promotes PI(4,5)P2 replenishment in response to TCR signaling during T cell development and survival","abstract":"Abstract Hydrolysis of phosphatidylinositol 4,5-bisphosphate (PIP 2 ) by phospholipase C-γ (PLCγ1) represents a critical step in T cell antigen receptor (TCR) signaling and subsequent thymocyte and T cell responses. PIP 2 replenishment following its depletion in the plasma membrane (PM) is dependent on delivery of its precursor phosphatidylinositol (PI) from the endoplasmic reticulum (ER) to the PM. We show that a PI transfer protein (PITP), Nir3 ( Pitpnm2 ), promotes PIP 2 replenishment following TCR stimulation and is important for T cell development. In Nir3 –/– T lineage cells, the PIP 2 replenishment following TCR stimulation is slower. Nir3 deficiency attenuates calcium mobilization in double-positive (DP) thymocytes in response to weak TCR stimulation. This impaired TCR signaling leads to attenuated thymocyte development at TCRβ selection and positive selection as well as diminished mature T cell fitness in Nir3 –/– mice. This study highlights the importance of PIP 2 replenishment mediated by PITPs at ER-PM junctions during TCR signaling.","journal":"Nature Immunology","year":2022,"id":257115,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":907559,"name":"Ynes Helou","orcid":null,"position":1,"is_corresponding":false},{"id":110103,"name":"Krishna Shrinivas","orcid":"0000-0002-4167-9385","position":2,"is_corresponding":false},{"id":494476,"name":"Jen Liou","orcid":"0000-0003-1546-3115","position":3,"is_corresponding":false},{"id":722335,"name":"Byron B. Au‐Yeung","orcid":"0000-0002-6446-9102","position":4,"is_corresponding":false},{"id":344120,"name":"Arthur Weiss","orcid":"0000-0002-2414-9024","position":5,"is_corresponding":false},{"id":371152,"name":"Wen Lu","orcid":"0000-0001-7363-386X","position":0,"is_corresponding":true}],"reference_count":60,"raw_metadata":null,"created_at":"2026-07-19T00:25:30.183987Z","pmid":"36581712","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":[]}