{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T12:25:18Z","timestamp":1791289518264,"version":"4.3.0"},"reference-count":56,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2007,2,19]]},"abstract":"<jats:p>A large proportion of Wiskott-Aldrich syndrome (WAS) patients develop autoimmunity and allergy. CD4+CD25+FOXP3+ natural regulatory T (nTreg) cells play a key role in peripheral tolerance to prevent immune responses to self-antigens and allergens. Therefore, we investigated the effect of WAS protein (WASP) deficiency on the distribution and suppressor function of nTreg cells. In WAS\u2212\/\u2212 mice, the steady-state distribution and phenotype of nTreg cells in the thymus and spleen were normal. However, WAS\u2212\/\u2212 nTreg cells engrafted poorly in immunized mice, indicating perturbed homeostasis. Moreover, WAS\u2212\/\u2212 nTreg cells failed to proliferate and to produce transforming growth factor \u03b2 upon T cell receptor (TCR)\/CD28 triggering. WASP-dependent F-actin polarization to the site of TCR triggering might not be involved in WAS\u2212\/\u2212 nTreg cell defects because this process was also inefficient in wild-type (WT) nTreg cells. Compared with WT nTreg cells, WAS\u2212\/\u2212 nTreg cells showed reduced in vitro suppressor activity on both WT and WAS\u2212\/\u2212 effector T cells. Similarly, peripheral nTreg cells were present at normal levels in WAS patients but failed to suppress proliferation of autologous and allogeneic CD4+ effector T cells in vitro. Thus, WASP appears to play an important role in the activation and suppressor function of nTreg cells, and a dysfunction or incorrect localization of nTreg cells may contribute to the development of autoimmunity in WAS patients.<\/jats:p>","DOI":"10.1084\/jem.20061334","type":"journal-article","created":{"date-parts":[[2007,2,12]],"date-time":"2007-02-12T20:22:32Z","timestamp":1171311752000},"page":"369-380","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":162,"title":["WASP regulates suppressor activity of human and murine CD4+CD25+FOXP3+ natural regulatory T cells"],"prefix":"10.1084","volume":"204","author":[{"given":"Francesco","family":"Marangoni","sequence":"first","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"},{"name":"2Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Trifari","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Scaramuzza","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Panaroni","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvana","family":"Martino","sequence":"additional","affiliation":[{"name":"3Department of Pediatrics, University of Turin, 10126 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi D.","family":"Notarangelo","sequence":"additional","affiliation":[{"name":"4Department of Pediatrics, University of Brescia, Spedali Civili, 25125 Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeina","family":"Baz","sequence":"additional","affiliation":[{"name":"5Department of Pediatrics, St. George Hospital University Medical Center, 1100 2807 Beirut, Lebanon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse","family":"Metin","sequence":"additional","affiliation":[{"name":"6SB Ankara Diskapi Children's Hospital, 06500 Ankara, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Cattaneo","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Villa","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"},{"name":"7Human Genome Department, Istituto di Tecnologie Biomediche, CNR ITB, 20090 Segrate, Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Aiuti","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Battaglia","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Grazia","family":"Roncarolo","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"},{"name":"2Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loi\u0308c","family":"Dupre\u0301","sequence":"additional","affiliation":[{"name":"1San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,2,12]]},"reference":[{"key":"2023072516033514500_BIB1","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","volume":"155","year":"1995","journal-title":"J. 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