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We previously showed that intranasal administration of recombinant Toxoplasma gondii serine protease inhibitor 1 (rTgPI-1) with ovalbumin alleviates asthma symptoms in mice. This study investigates the immunomodulatory mechanisms of rTgPI-1, focusing on its effect on dendritic cells (DCs). Bone marrow-derived DCs (BMDCs) were generated in the presence of rTgPI-1 and analyzed for their phenotype. rTgPI-1 exposed BMDCs showed reduced CD80, CD86, and MHCII, increased PDL-1 and CD45Rb, and a higher IL-10\/IL-12 ratio. These BMDCs induced fewer CD69\u207aCD4\u207a T cells, decreased proliferation and secretion of IL-17 and IL-4, and increased CD4\u207aFoxP3\u207a T cells. In vivo, intranasal co-administration of rTgPI-1 with allergen in asthmatic mice reduced CD80high\/CD86high DCs, expanded lung CD4\u207aFoxP3\u207a regulatory T cells, and decreased the cDC2 subset, correlating with reduced IL-4 levels. Importantly, nafamostat mesylate\u2014a synthetic serine protease inhibitor previously shown to alleviate asthma symptoms\u2014failed to induce FoxP3\u207a T cells both in vitro and in vivo, underscoring the unique tolerogenic activity of rTgPI-1. Finally, stimulation of peripheral blood mononuclear cells from mite-allergic patients with house dust mite extract in the presence of rTgPI-1 led to reduced allergen-specific IL-4 and IL-5 secretion. These findings demonstrate that rTgPI-1 promotes a semimature, tolerogenic DC phenotype, suppresses T cell activation, and fosters regulatory T cell differentiation. Moreover, rTgPI-1 selectively modulates DC subsets in vivo. The observed effects on patient-derived PBMCs support its potential for further preclinical development as an adjuvant for allergen-specific immunotherapy.<\/jats:p>","DOI":"10.1093\/intimm\/dxaf034","type":"journal-article","created":{"date-parts":[[2025,6,7]],"date-time":"2025-06-07T07:43:53Z","timestamp":1749282233000},"page":"695-710","source":"Crossref","is-referenced-by-count":4,"title":["Modulating dendritic cell function in allergic asthma with\n                    <i>Toxoplasma gondii<\/i>\n                    serine protease inhibitor 1"],"prefix":"10.1093","volume":"37","author":[{"given":"Joel","family":"Katan Pi\u00f1eiro","sequence":"first","affiliation":[{"name":"Centro de Estudios en Salud y Medio Ambiente, ITECA, ECyT, UNSAM, CONICET , Buenos Aires ,","place":["Argentina"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ariadna Soledad","family":"Soto","sequence":"additional","affiliation":[{"name":"Department of Immunology, University of Pittsburgh , 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