{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:18:51Z","timestamp":1791274731127,"version":"4.1.0"},"reference-count":86,"publisher":"Rockefeller University Press","issue":"2","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,2,9]]},"abstract":"<jats:p>Patients with ectodermal dysplasia with immunodeficiency (ED-ID) caused by mutations in the inhibitor of NF-\u03baB \u03b1 (I\u03baB\u03b1) are susceptible to severe recurrent infections, despite normal T and B cell numbers and intact in vitro lymphocyte function. Moreover, the outcome of hematopoietic stem cell transplantation (HSCT) in these patients is poor despite good engraftment. Mice heterozygous for the I\u03baB\u03b1 S32I mutation found in patients exhibited typical features of ED-ID. Strikingly, the mice lacked lymph nodes, Peyer\u2019s patches, splenic marginal zones, and follicular dendritic cells and failed to develop contact hypersensitivity (CHS) or form germinal centers (GCs), all features not previously recognized in patients and typical of defective noncanonical NF-\u03baB signaling. Lymphotoxin \u03b2 receptor (LT\u03b2R)\u2013driven induction of chemokines and adhesion molecules mediated by both canonical and noncanonical NF-\u03baB pathways was impaired, and levels of p100 were markedly diminished in the mutant. I\u03baB\u03b1 mutant\u2192Rag2\u2212\/\u2212, but not WT\u2192I\u03baB\u03b1 mutant, bone marrow chimeras formed proper lymphoid organs and developed CHS and GCs. Defective architectural cell function explains the immunodeficiency and poor outcome of HSCT in patients with I\u03baB\u03b1 deficiency and suggests that correction of this niche is critical for reconstituting their immune function.<\/jats:p>","DOI":"10.1084\/jem.20140979","type":"journal-article","created":{"date-parts":[[2015,1,20]],"date-time":"2015-01-20T02:58:06Z","timestamp":1421722686000},"page":"185-202","update-policy":"https:\/\/doi.org\/10.1084\/jem.crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Defective lymphoid organogenesis underlies the immune deficiency caused by a heterozygous S32I mutation in I\u03baB\u03b1"],"prefix":"10.1084","volume":"212","author":[{"given":"Jana L.","family":"Mooster","sequence":"first","affiliation":[{"name":"Division of Allergy and Immunology 1 and 2"},{"name":"Program in Cellular and Molecular Medicine, Boston Children\u2019s Hospital, Boston, MA 02115 1 and 2"},{"name":"Department of Pediatrics 3 , 4 , and 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