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Hyperresponsiveness and altered tolerogenicity of DCs contribute to the development and pathogenesis of system lupus erythematosus (SLE); therefore, DC-targeted therapies aimed at inducing specific immune tolerance have become of great importance for the treatment of SLE. This study developed a new nanoparticle (NP) containing a biodegradable PDMAEMA-PLGA copolymer for target-oriented delivery to DCs in situ. PDMAEMA-PLGA NPs provided sustained drug release and exhibited immunosuppressive activity in FLT3L and GM-CSF-derived bone marrow in conventional DCs (BM-cDCs). PDMAEMA-PLGA NPs improved dexamethasone capability to convert wild-type and Fcgr2b-\/- BM-cDCs from an immunogenic to tolerogenic state, and BM-cDCs treated with dexamethasone-incorporated PDMAEMA-PLGA NPs (Dex-NPs) efficiently mediated regulatory T cell (Treg) expansion in vitro. Dex-NP therapy potentially alleviated lupus disease in Fcgr2b-\/- mice by mediating Foxp3+ Treg expansion in an antigen-specific manner. Our findings substantiate the superior efficacy of DC-targeted therapy using the PDMAEMA-PLGA NP delivery system and provide further support for clinical development as a potential therapy for SLE. Furthermore, PDMAEMA-PLGA NP may be a versatile platform for DC-targeted therapy to induce antigen-specific immune tolerance to unwanted immune responses that occur in autoimmune disease, allergy, and transplant rejection.<\/jats:p>","DOI":"10.3390\/ijms24098313","type":"journal-article","created":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T09:18:09Z","timestamp":1683278289000},"page":"8313","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Immunosuppressive Polymeric Nanoparticles Targeting Dendritic Cells Alleviate Lupus Disease in Fcgr2b-\/- Mice by Mediating Antigen-Specific Immune Tolerance"],"prefix":"10.3390","volume":"24","author":[{"given":"Phuriwat","family":"Khiewkamrop","sequence":"first","affiliation":[{"name":"Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center 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Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Warerat","family":"Kaewduangduen","sequence":"additional","affiliation":[{"name":"Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Opor","family":"Sonpoung","sequence":"additional","affiliation":[{"name":"Oral Biology Research Center, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kasirapat","family":"Ariya-anandech","sequence":"additional","affiliation":[{"name":"Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattiya","family":"Hirankarn","sequence":"additional","affiliation":[{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Immunology Unit, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1392-4061","authenticated-orcid":false,"given":"Patcharee","family":"Ritprajak","sequence":"additional","affiliation":[{"name":"Research Unit in Integrative Immuno-Microbial Biochemistry and Bioresponsive Nanomaterials, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Department of Microbiology, Faculty of Dentistry, Chulalongkorn University, Bangkok 10330, 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