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Pathogenic Th2 cells are a major driver for disease, and allergen\u2010specific immunotherapies (AIT) aim to increase the allergen threshold required to elicit severe allergic symptoms. However, the majority of AIT approaches require lengthy treatments and convey transient disease suppression, likely due to insufficient targeting of pathogenic Th2 responses. Here, the ability of allergen\u2010encapsulating nanoparticles to directly suppress pathogenic Th2 responses and reactivity is investigated in a mouse model of food allergy. NPs associate with pro\u2010tolerogenic antigen presenting cells, provoking accumulation of antigen\u2010specific, functionally suppressive regulatory T cells in the small intestine lamina propria. Two intravenous doses of allergen encapsulated in poly(lactide\u2010co\u2010glycolide) nanoparticles (NPs) significantly reduces oral food challenge (OFC)\u2010induced anaphylaxis. Importantly, NP treatment alters the fates of pathogenic allergen\u2010specific Th2 cells, reprogramming these cells toward CD25<jats:sup>+<\/jats:sup>FoxP3<jats:sup>+<\/jats:sup> regulatory and CD73<jats:sup>+<\/jats:sup>FR4<jats:sup>+<\/jats:sup> anergic phenotypes. NP\u2010mediated reductions in the frequency of effector cells in the gut and mast cell degranulation following OFC are also demonstrated. These studies reveal mechanisms by which an allergen\u2010encapsulating NP therapy and, more broadly, allergen\u2010specific immunotherapies, can rapidly attenuate allergic responses by targeting pathogenic Th2 cells.<\/jats:p>","DOI":"10.1002\/adhm.202400237","type":"journal-article","created":{"date-parts":[[2024,5,1]],"date-time":"2024-05-01T15:52:55Z","timestamp":1714578775000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Allergen\u2010Encapsulating Nanoparticles Reprogram Pathogenic Allergen\u2010Specific Th2 Cells to Suppress Food Allergy"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5261-6355","authenticated-orcid":false,"given":"Michael N.","family":"Saunders","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laila M.","family":"Rad","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura A.","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey J.","family":"Landers","sequence":"additional","affiliation":[{"name":"Mary H. 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Weiser Food Allergy Center University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate V.","family":"Griffin","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian C.","family":"Ross","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles A.","family":"Parkos","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asma","family":"Nusrat","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan  Ann Arbor MI 48109 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen D.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2010Immunology Northwestern University  Chicago IL 60611 USA"},{"name":"Center for Human Immunobiology Northwestern University  Chicago IL 60611 USA"},{"name":"Interdepartmental Immunobiology Center Feinberg School of Medicine Northwestern University  Chicago IL 60611 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph R.","family":"Podojil","sequence":"additional","affiliation":[{"name":"Department of Microbiology\u2010Immunology Northwestern University  Chicago IL 60611 USA"},{"name":"Center for Human Immunobiology Northwestern University  Chicago IL 60611 USA"},{"name":"Cour Pharmaceuticals Development Company  Northbrook IL 60077 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1455-0586","authenticated-orcid":false,"given":"Jessica J.","family":"O'Konek","sequence":"additional","affiliation":[{"name":"Mary H. 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