{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lui VG"],"funding":["National Institute of Arthritis and Musculoskeletal and Skin Diseases","NIDDK NIH HHS","Immunology Training Program","NIAID NIH HHS","NCI NIH HHS","Jeffrey Modell Foundation","Kennedy Trust","NIAMS NIH HHS","Wellcome Trust","Cancer Research Institute","National Science Foundation"],"pagination":["e20230927"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10644909"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["221(1)"],"pubmed_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 resi"],"journal":["The Journal of experimental medicine"],"pubmed_title":["A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation."],"pmcid":["PMC10644909"],"funding_grant_id":["P30 CA046934","P30 DK116073","CRI4503","100262Z/12/Z","K23 AR070897","K23AR070897","KENN202117","DGE-1938058","224343/Z/21/Z","T32 AI07405","T32 AI007405","KENN202114"],"pubmed_authors":["Acharya A","Jacobsen EM","Capera J","Minguet S","Lundquist K","Dustin ML","Baxter RM","Cambier JC","Gumbart JC","Pannicke U","Hoenig M","Schwarz K","Lui VG","Cabrera-Martinez B","Hartl FA","Garcia-Perez JE","Matusewicz P","Niewolik D","Schamel WW","D'Abramo M","Debatin KM","Lorenz M","Schulz AS","Bailey O","Alba J","Hsieh EWY"],"additional_accession":[]},"is_claimable":false,"name":"A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.","description":"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 resi","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jan","modification":"2026-07-14T18:38:30.722Z","creation":"2024-11-09T11:16:28.796Z"},"accession":"S-EPMC10644909","cross_references":{"pubmed":["37962568"],"doi":["10.1084/jem.20230927"]}}