{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T05:06:37Z","timestamp":1790053597999,"version":"4.0.1"},"reference-count":36,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006447","name":"Stiftung f\u00fcr wissenschaftliche Forschung an der Universit\u00e4t Z\u00fcrich\/Erbschaft B\u00fchler","doi-asserted-by":"publisher","award":["UZH STEB-21-005"],"award-info":[{"award-number":["UZH STEB-21-005"]}],"id":[{"id":"10.13039\/501100006447","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Julius-M\u00fcller Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>T-cells are major therapeutic targets in cancer and immune-mediated diseases. Their development and differentiation require highly dynamic receptor turnover. Protein tyrosine phosphatase non-receptor type 23 (PTPN23) encodes a ubiquitously expressed pseudophosphatase involved in trafficking and internalization of specific cell receptors. Although PTPN23 has essential functions in several cell types, its role in T-cells remains unknown. We therefore investigated the role of PTPN23 in T-cells. We generated transgenic mice lacking PTPN23 specifically in T-cells (PTPN23-CD4-Cre). Flow cytometry, single-cell RNA sequencing (scRNA-seq), and proteomic analysis were performed in lymphoid and mucosal organs. PTPN23-CD4-Cre mice exhibited a significant reduction in total T-cell numbers in lymphoid organs, accompanied by increased proportions and numbers of \u03b3\u03b4 T-cells and markedly reduced na\u00efve T-cells. Similar findings were made in mucosal organs, with \u03b3\u03b4 T-cell levels rising as age increased. In vitro functional assays revealed that residual PTPN23-CD4-Cre T-cells display an altered cytokine profile enriched for inflammatory mediators, a finding that was accompanied by proteomic and phosphoproteomic alterations consistent with changes in T-cell differentiation and inflammatory programs. scRNA-seq analysis showed altered representation of thymocytes along a shared developmental trajectory, with enrichment of PTPN23-deficient T-cells at earlier developmental states. Our study identifies PTPN23 as a previously unrecognized player of T-cell development, differentiation, and immune homeostasis.<\/jats:p>","DOI":"10.3390\/cells15181694","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1694","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["T-Cell Specific Deletion of PTPN23 Alters T-Cell Development and TCR\u03b1\u03b2\/\u03b3\u03b4 Composition"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3801-0441","authenticated-orcid":false,"given":"Rocio","family":"Sanchez Alvarez","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Madita","family":"Determann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Luise","family":"Linzmeier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6554-0239","authenticated-orcid":false,"given":"Marijn","family":"Wilmink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6937-5745","authenticated-orcid":false,"given":"Maria Rae","family":"Walker","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4207-0968","authenticated-orcid":false,"given":"Anna","family":"Bircher","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1415-6674","authenticated-orcid":false,"given":"C\u00e9line","family":"Mamie","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8835-5210","authenticated-orcid":false,"given":"Doris","family":"P\u00f6hlmann","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1288-0706","authenticated-orcid":false,"given":"Marlene","family":"Schwarzfischer","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Sebastian","family":"Zeissig","sequence":"additional","affiliation":[{"name":"Department of Visceral Surgery and Medicine, University Hospital Bern, 3010 Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6045-0228","authenticated-orcid":false,"given":"Claudia","family":"Gottier","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1216-899X","authenticated-orcid":false,"given":"Silvia","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-0058","authenticated-orcid":false,"given":"Marianne R.","family":"Spalinger","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, R\u00e4mistrasse 100, 8091 Z\u00fcrich, 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