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Current treatment modalities focus on the reduction of disease symptoms using anti-inflammatory drugs which can lead to side effects due to systemic immune suppression. Restoration of immune tolerance by down-regulating auto-reactive cells in an antigen-specific manner is currently the \u201choly grail\u201d for the treatment of autoimmune diseases. A promising strategy is the use of nanoparticles that can deliver antigens to antigen-presenting cells which in turn can enhance antigen-specific regulatory T cells. In this review, we highlight some promising cell targets (e.g. liver sinusoidal endothelial cells and splenic marginal zone macrophages) for exploiting natural immune tolerance processes, and several strategies by which antigen-carrying nanoparticles can target these cells. We also discuss how nanoparticles carrying immunomodulators may be able to activate tolerance in other antigen-presenting cell types. Finally, we discuss some important aspects that must be taken into account when translating data from animal studies to patients.<\/jats:p>","DOI":"10.3389\/fimmu.2022.864403","type":"journal-article","created":{"date-parts":[[2022,3,28]],"date-time":"2022-03-28T12:49:10Z","timestamp":1648471750000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":54,"title":["Nanoparticles for Inducing Antigen-Specific T Cell Tolerance in Autoimmune Diseases"],"prefix":"10.3389","volume":"13","author":[{"given":"Naomi","family":"Benne","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00eblle","family":"ter Braake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arie Jan","family":"Stoppelenburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Femke","family":"Broere","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.1016\/j.jaci.2009.12.980","article-title":"Overview of the Immune Response","volume":"125","author":"Chaplin","year":"2010","journal-title":"J Allergy Clin Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2017.107","article-title":"Antigen-Specific Immunotherapies in Rheumatic Diseases","volume":"13","author":"Pozsgay","year":"2017","journal-title":"Nat Rev Rheumatol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.biochi.2020.03.014","article-title":"Regulatory T Cells in Patients With Early Untreated Rheumatoid Arthritis: Phenotypic Changes in the Course of Methotrexate Treatment","volume":"174","author":"Avdeeva","year":"2020","journal-title":"Biochimie"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/86302","article-title":"Thymic Selection of CD4+CD25+ Regulatory T Cells Induced by an Agonist Self-Peptide","volume":"2","author":"Jordan","year":"2001","journal-title":"Nat Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00152","article-title":"Generation and Function of Induced Regulatory T Cells","volume":"4","author":"Schmitt","year":"2013","journal-title":"Front Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00623","article-title":"Translating Treg Therapy in Humanized Mice","volume":"6","author":"Hahn","year":"2015","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0324-7","article-title":"Transcriptional and Epigenetic Basis of Treg Cell Development and Function: Its Genetic Anomalies or Variations in Autoimmune Diseases","volume":"30","author":"Ohkura","year":"2020","journal-title":"Cell Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.03100","article-title":"Treg Heterogeneity, Function, and Homeostasis","volume":"10","author":"Shevyrev","year":"2019","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3179","article-title":"Coexpression of CD49b and LAG-3 Identifies Human and Mouse T Regulatory Type 1 Cells","volume":"19","author":"Gagliani","year":"2013","journal-title":"Nat Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.1.179","article-title":"Th3 Cells in Peripheral Tolerance. 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