{"doi":"10.1084/jem.20230927","title":"A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation","abstract":"Lymphocyte-specific protein tyrosine kinase (LCK) is essential for T cell antigen receptor (TCR)-mediated signal transduction. Here, we report two siblings homozygous for a novel LCK variant (c.1318C>T; P440S) characterized by T cell lymphopenia with skewed memory phenotype, infant-onset recurrent infections, failure to thrive, and protracted diarrhea. The patients' T cells show residual TCR signal transduction and proliferation following anti-CD3/CD28 and phytohemagglutinin (PHA) stimulation. We demonstrate in mouse models that complete (Lck-/-) versus partial (LckP440S/P440S) loss-of-function LCK causes disease with differing phenotypes. While both Lck-/- and LckP440S/P440S mice exhibit arrested thymic T cell development and profound T cell lymphopenia, only LckP440S/P440S mice show residual T cell proliferation, cytokine production, and intestinal inflammation. Furthermore, the intestinal disease in the LckP440S/P440S mice is prevented by CD4+ T cell depletion or regulatory T cell transfer. These findings demonstrate that P440S LCK spares sufficient T cell function to allow the maturation of some conventional T cells but not regulatory T cells-leading to intestinal inflammation.","journal":"The Journal of Experimental Medicine","year":2023,"id":337765,"datarank":0.44166584687496613,"base_score":2.9444389791664403,"endowment":2.9444389791664403,"self_citation_contribution":0.44166584687496613,"citation_network_contribution":0.0,"self_endowment_contribution":0.44166584687496613,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1069694,"name":"Manfred Hoenig","orcid":"0000-0001-9165-1690","position":1,"is_corresponding":false},{"id":1069695,"name":"Berenice Cabrera-Martinez","orcid":"0009-0000-2919-2729","position":2,"is_corresponding":false},{"id":558538,"name":"Ryan M. Baxter","orcid":"0000-0002-2235-6193","position":3,"is_corresponding":false},{"id":1069696,"name":"Josselyn E. Garcia‐Perez","orcid":"0000-0003-2369-532X","position":4,"is_corresponding":false},{"id":1069697,"name":"Olivia Bailey","orcid":"0009-0007-5258-9856","position":5,"is_corresponding":false},{"id":322891,"name":"Atanu Acharya","orcid":"0000-0002-6960-7789","position":6,"is_corresponding":false},{"id":341878,"name":"Karl Lundquist","orcid":"0000-0002-3418-8342","position":7,"is_corresponding":false},{"id":1069698,"name":"Jesusa Capera","orcid":"0000-0002-8123-7725","position":8,"is_corresponding":false},{"id":1069699,"name":"Paul Matusewicz","orcid":"0009-0003-8879-7535","position":9,"is_corresponding":false},{"id":1069700,"name":"Frederike A. Hartl","orcid":"0000-0003-3538-5214","position":10,"is_corresponding":false},{"id":1069701,"name":"Marco D’Abramo","orcid":"0000-0001-6020-8581","position":11,"is_corresponding":false},{"id":1069702,"name":"Josephine Alba","orcid":"0000-0002-5467-4751","position":12,"is_corresponding":false},{"id":517472,"name":"Eva‐Maria Jacobsen","orcid":"0000-0003-4750-0136","position":13,"is_corresponding":false},{"id":1070213,"name":"Doris Niewolik","orcid":"0000-0001-6055-1451","position":14,"is_corresponding":false},{"id":1069703,"name":"Myriam Ricarda Lorenz","orcid":"0000-0002-3537-4550","position":15,"is_corresponding":false},{"id":1034626,"name":"Ulrich Pannicke","orcid":"0000-0002-0929-1794","position":16,"is_corresponding":false},{"id":490855,"name":"Ansgar Schulz","orcid":"0000-0002-7798-7996","position":17,"is_corresponding":false},{"id":348712,"name":"Klaus‐Michael Debatin","orcid":"0000-0002-8397-1886","position":18,"is_corresponding":false},{"id":1001298,"name":"Wolfgang W. Schamel","orcid":"0000-0003-4496-3100","position":19,"is_corresponding":false},{"id":1001297,"name":"Susana Minguet","orcid":"0000-0001-8211-5538","position":20,"is_corresponding":false},{"id":98033,"name":"James C. Gumbart","orcid":"0000-0002-1510-7842","position":21,"is_corresponding":false},{"id":61554,"name":"Michael L. Dustin","orcid":"0000-0003-4983-6389","position":22,"is_corresponding":false},{"id":411835,"name":"John C. Cambier","orcid":"0000-0002-7803-242X","position":23,"is_corresponding":false},{"id":1034662,"name":"Klaus Schwarz","orcid":"0000-0003-3178-5990","position":24,"is_corresponding":false},{"id":231988,"name":"Elena W.Y. Hsieh","orcid":"0000-0003-3969-6597","position":25,"is_corresponding":false},{"id":1069693,"name":"Victor G Lui","orcid":"0000-0003-1553-1499","position":0,"is_corresponding":true}],"reference_count":108,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:10:31.133446Z","pmid":"37962568","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":[]}