{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:44:16Z","timestamp":1792730656586,"version":"4.5.0"},"reference-count":51,"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>The Wiskott-Aldrich syndrome, a primary human immunodeficiency, results from defective expression of the hematopoietic-specific cytoskeletal regulator Wiskott-Aldrich syndrome protein (WASP). Because CD4+CD25+Foxp3+ naturally occurring regulatory T (nTreg) cells control autoimmunity, we asked whether colitis in WASP knockout (WKO) mice is associated with aberrant development\/function of nTreg cells. We show that WKO mice have decreased numbers of CD4+CD25+Foxp3+ nTreg cells in both the thymus and peripheral lymphoid organs. Moreover, we demonstrate that WKO nTreg cells are markedly defective in both their ability to ameliorate the colitis induced by the transfer of CD45RBhi T cells and in functional suppression assays in vitro. Compared with wild-type (WT) nTreg cells, WKO nTreg cells show significantly impaired homing to both mucosal (mesenteric) and peripheral sites upon adoptive transfer into WT recipient mice. Suppression defects may be independent of antigen receptor\u2013mediated actin rearrangement because both WT and WKO nTreg cells remodeled their actin cytoskeleton inefficiently upon T cell receptor stimulation. Preincubation of WKO nTreg cells with exogenous interleukin (IL)-2, combined with antigen receptor\u2013mediated activation, substantially rescues the suppression defects. WKO nTreg cells are also defective in the secretion of the immunomodulatory cytokine IL-10. Overall, our data reveal a critical role for WASP in nTreg cell function and implicate nTreg cell dysfunction in the autoimmunity associated with WASP deficiency.<\/jats:p>","DOI":"10.1084\/jem.20061338","type":"journal-article","created":{"date-parts":[[2007,2,12]],"date-time":"2007-02-12T20:22:32Z","timestamp":1171311752000},"page":"381-391","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":176,"title":["The Wiskott-Aldrich syndrome protein is required for the function of CD4+CD25+Foxp3+ regulatory T cells"],"prefix":"10.1084","volume":"204","author":[{"given":"Michel H.","family":"Maillard","sequence":"first","affiliation":[{"name":"1Gastrointestinal Unit,"},{"name":"5Department of Medicine and"},{"name":"7Division of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinicius","family":"Cotta-de-Almeida","sequence":"additional","affiliation":[{"name":"1Gastrointestinal Unit,"},{"name":"5Department of Medicine and"},{"name":"8Department of Ultrastructure and Cell Biology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 21040-360 Rio de Janeiro, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuminao","family":"Takeshima","sequence":"additional","affiliation":[{"name":"1Gastrointestinal Unit,"},{"name":"5Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deanna D.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"1Gastrointestinal Unit,"},{"name":"5Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Michetti","sequence":"additional","affiliation":[{"name":"7Division of Gastroenterology and Hepatology, Department of Medicine, Lausanne University Hospital, 1005 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn","family":"Nagler","sequence":"additional","affiliation":[{"name":"2Division of Rheumatology,"},{"name":"3Allergy and Immunology, and"},{"name":"5Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atul K.","family":"Bhan","sequence":"additional","affiliation":[{"name":"4Immunopathology Unit and the Center for the Study of Inflammatory Bowel Diseases, Massachusetts General Hospital, Boston, MA 02114"},{"name":"6Department of Pathology, Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott B.","family":"Snapper","sequence":"additional","affiliation":[{"name":"1Gastrointestinal Unit,"},{"name":"5Department of Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2007,2,12]]},"reference":[{"key":"2023072516070388400_BIB1","doi-asserted-by":"crossref","first-page":"e622","DOI":"10.1542\/peds.111.5.e622","volume":"111","year":"2003","journal-title":"Pediatrics."},{"key":"2023072516070388400_BIB2","doi-asserted-by":"crossref","first-page":"1658","DOI":"10.4049\/jimmunol.173.3.1658","volume":"173","year":"2004","journal-title":"J. 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