{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:53:53Z","timestamp":1791294833246,"version":"4.1.0"},"reference-count":31,"publisher":"Rockefeller University Press","issue":"4","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2009,4,13]]},"abstract":"<jats:p>The Wiskott-Aldrich syndrome (WAS) protein (WASp) is a regulator of actin cytoskeleton in hematopoietic cells. Mutations of the WASp gene cause WAS. Although WASp is involved in various immune cell functions, its role in invariant natural killer T (iNKT) cells has never been investigated. Defects of iNKT cells could indeed contribute to several WAS features, such as recurrent infections and high tumor incidence. We found a profound reduction of circulating iNKT cells in WAS patients, directly correlating with the severity of clinical phenotype. To better characterize iNKT cell defect in the absence of WASp, we analyzed was\u2212\/\u2212 mice. iNKT cell numbers were significantly reduced in the thymus and periphery of was\u2212\/\u2212 mice as compared with wild-type controls. Moreover analysis of was\u2212\/\u2212 iNKT cell maturation revealed a complete arrest at the CD44+ NK1.1\u2212 intermediate stage. Notably, generation of BM chimeras demonstrated a was\u2212\/\u2212 iNKT cell-autonomous developmental defect. was\u2212\/\u2212 iNKT cells were also functionally impaired, as suggested by the reduced secretion of interleukin 4 and interferon \u03b3 upon in vivo activation. Altogether, these results demonstrate the relevance of WASp in integrating signals critical for development and functional differentiation of iNKT cells and suggest that defects in these cells may play a role in WAS pathology.<\/jats:p>","DOI":"10.1084\/jem.20081773","type":"journal-article","created":{"date-parts":[[2009,3,24]],"date-time":"2009-03-24T01:09:54Z","timestamp":1237856994000},"page":"735-742","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["The Wiskott-Aldrich syndrome protein is required for iNKT cell maturation and function"],"prefix":"10.1084","volume":"206","author":[{"given":"Michela","family":"Locci","sequence":"first","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy 1"},{"name":"Tor Vergata University, 00133 Rome, Italy 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University Medical Center, 2300 RC Leiden, Netherlands 6"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian J.","family":"Thrasher","sequence":"additional","affiliation":[{"name":"Institute of Child Health, University College London and Great Ormond Street Hospital for Children, WCIN 1EH London, England, UK 7"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ansgar","family":"Schulz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, University Hospital Ulm, 89075 Ulm, Germany 8"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Litzman","sequence":"additional","affiliation":[{"name":"Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, St. Anne's University Hospital, 656 91 Brno, Czech Republic 9"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Roncarolo","sequence":"additional","affiliation":[{"name":"Vita-Salute San Raffaele University, 20132 Milan, Italy 1"},{"name":"San Raffaele Telethon Institute for Gene Therapy, 20132 Milan, Italy 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Casorati","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, Dipartimento di Biotecnologie, San Raffaele Scientific Institute, 20132 Milan, Italy 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Dellabona","sequence":"additional","affiliation":[{"name":"Experimental Immunology Unit, Cancer Immunotherapy and Gene Therapy Program, Dipartimento di Biotecnologie, San Raffaele Scientific Institute, 20132 Milan, Italy 10"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Villa","sequence":"additional","affiliation":[{"name":"San Raffaele Telethon Institute for 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