{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:06:50Z","timestamp":1772118410880,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["016.186.116"],"award-info":[{"award-number":["016.186.116"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["917.13.338"],"award-info":[{"award-number":["917.13.338"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Invariant natural killer T cells (iNKT) constitute up to 50% of liver lymphocytes and contribute to immunosurveillance as well as pathogenesis of the liver. Systemic activation of iNKT cells induces acute immune\u2010mediated liver injury. However, how tissue damage events regulate iNKT cell function and homeostasis remains unclear. We found that specifically tissue\u2010resident iNKT cells in liver and spleen express the tissue\u2010damage receptor P2RX7 and the P2RX7\u2010activating ectoenzyme ARTC2. P2RX7 expression restricted formation of iNKT cells in the liver suggesting that liver iNKT cells are actively restrained under homeostatic conditions. Deliberate activation of P2RX7 in vivo by exogenous NAD resulted in a nearly complete iNKT cell ablation in liver and spleen in a P2RX7\u2010dependent manner. Tissue damage generated by acetaminophen\u2010induced liver injury reduced the number of iNKT cells in the liver. The tissue\u2010damage\u2010induced iNKT cell depletion was driven by P2RX7 and localized to the site of injury, as iNKT cells in the spleen remained intact. The depleted liver iNKT cells reconstituted only slowly compared to other lymphocytes such as regulatory T cells. These findings suggest that tissue\u2010damage\u2010mediated depletion of iNKT cells acts as a feedback mechanism to limit iNKT cell\u2010induced pathology resulting in the establishment of a tolerogenic environment.<\/jats:p>","DOI":"10.1002\/eji.201948509","type":"journal-article","created":{"date-parts":[[2020,5,11]],"date-time":"2020-05-11T01:23:55Z","timestamp":1589160235000},"page":"1515-1524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Murine iNKT cells are depleted by liver damage via activation of P2RX7"],"prefix":"10.1002","volume":"50","author":[{"given":"Astrid A.","family":"Bovens","sequence":"first","affiliation":[{"name":"Department of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Wesselink","sequence":"additional","affiliation":[{"name":"Department of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix M.","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Experimental Immunology Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natasja A. M.","family":"Kragten","sequence":"additional","affiliation":[{"name":"Department of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ren\u00e9 A. W.","family":"van Lier","sequence":"additional","affiliation":[{"name":"Department of Hematopoiesis Sanquin Research and Landsteiner Laboratory Amsterdam UMC University of Amsterdam  Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3623-7555","authenticated-orcid":false,"given":"Klaas P. J. 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