{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T02:13:51Z","timestamp":1792721631651,"version":"4.5.0"},"reference-count":82,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"91","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Immunol."],"published-print":{"date-parts":[[2024,1,19]]},"abstract":"<jats:p>\n                    Allergic diseases are common, affecting more than 20% of the population. Genetic variants in the TGF\u03b2 pathway are strongly associated with atopy. To interrogate the mechanisms underlying this association, we examined patients and mice with Loeys-Dietz syndrome (LDS) who harbor missense mutations in the kinase domain of\n                    <jats:italic>TGF\u0392R1\/2<\/jats:italic>\n                    . We demonstrate that LDS mutations lead to reduced TGF\u03b2 signaling and elevated total and allergen-specific IgE, despite the presence of wild-type T regulatory cells in a chimera model. Germinal center activity was enhanced in LDS and characterized by a selective increase in type 2 follicular helper T cells (T\n                    <jats:sub>FH<\/jats:sub>\n                    2). Expression of\n                    <jats:italic>Pik3cg<\/jats:italic>\n                    was increased in LDS T\n                    <jats:sub>FH<\/jats:sub>\n                    cells and associated with reduced levels of the transcriptional repressor SnoN. PI3K\u03b3\/mTOR signaling in LDS na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells was elevated after T cell receptor cross-linking, and pharmacologic inhibition of PI3K\u03b3 or mTOR prevented exaggerated T\n                    <jats:sub>FH<\/jats:sub>\n                    2 and antigen-specific IgE responses after oral antigen exposure in an adoptive transfer model. Na\u00efve CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells from nonsyndromic allergic individuals also displayed decreased TGF\u03b2 signaling, suggesting that our mechanistic discoveries may be broadly relevant to allergic patients in general. Thus, TGF\u03b2 plays a conserved, T cell\u2013intrinsic, and nonredundant role in restraining T\n                    <jats:sub>FH<\/jats:sub>\n                    2 development via the PI3K\u03b3\/mTOR pathway and thereby protects against allergic disease.\n                  <\/jats:p>","DOI":"10.1126\/sciimmunol.adg8691","type":"journal-article","created":{"date-parts":[[2024,1,19]],"date-time":"2024-01-19T13:58:49Z","timestamp":1705672729000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":28,"title":["TGF\u03b2 prevents IgE-mediated allergic disease by restraining T follicular helper 2 differentiation"],"prefix":"10.1126","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4436-9558","authenticated-orcid":true,"given":"Tamara T.","family":"Haque","sequence":"first","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1632-4336","authenticated-orcid":true,"given":"Katherine A.","family":"Weissler","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3403-6824","authenticated-orcid":true,"given":"Zoe","family":"Schmiechen","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8197-3941","authenticated-orcid":true,"given":"Karen","family":"Laky","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniella M.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Li","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Locci","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7316-3044","authenticated-orcid":true,"given":"Mathilde","family":"Turfkruyer","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6852-5661","authenticated-orcid":true,"given":"Chen","family":"Yao","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Schaughency","sequence":"additional","affiliation":[{"name":"Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lashawna","family":"Leak","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Lack","sequence":"additional","affiliation":[{"name":"Collaborative Bioinformatics Resource, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5668-9319","authenticated-orcid":true,"given":"Yuka","family":"Kanno","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-9752","authenticated-orcid":true,"given":"John","family":"O\u2019Shea","sequence":"additional","affiliation":[{"name":"Laboratory of Lymphocyte Nuclear Biology, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pamela A.","family":"Frischmeyer-Guerrerio","sequence":"additional","affiliation":[{"name":"Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, 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