{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T03:30:25Z","timestamp":1792639825390,"version":"4.5.0"},"reference-count":303,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T00:00:00Z","timestamp":1616976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Autoimmune diseases affect roughly 5-10% of the total population, with women affected more than men. The standard treatment for autoimmune or autoinflammatory diseases had long been immunosuppressive agents until the advent of immunomodulatory biologic drugs, which aimed at blocking inflammatory mediators, including proinflammatory cytokines. At the frontier of these biologic drugs are TNF-\u03b1 blockers. These therapies inhibit the proinflammatory action of TNF-\u03b1 in common autoimmune diseases such as rheumatoid arthritis, psoriasis, ulcerative colitis, and Crohn\u2019s disease. TNF-\u03b1 blockade quickly became the \u201cstandard of care\u201d for these autoimmune diseases due to their effectiveness in controlling disease and decreasing patient\u2019s adverse risk profiles compared to broad-spectrum immunosuppressive agents. However, anti-TNF-\u03b1 therapies have limitations, including known adverse safety risk, loss of therapeutic efficacy due to drug resistance, and lack of efficacy in numerous autoimmune diseases, including multiple sclerosis. The next wave of truly transformative therapeutics should aspire to provide a cure by selectively suppressing pathogenic autoantigen-specific immune responses while leaving the rest of the immune system intact to control infectious diseases and malignancies. In this review, we will focus on three main areas of active research in immune tolerance. First, tolerogenic vaccines aiming at robust, lasting autoantigen-specific immune tolerance. Second, T cell therapies using Tregs (either polyclonal, antigen-specific, or genetically engineered to express chimeric antigen receptors) to establish active dominant immune tolerance or T cells (engineered to express chimeric antigen receptors) to delete pathogenic immune cells. Third, IL-2 therapies aiming at expanding immunosuppressive regulatory T cells\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.657768","type":"journal-article","created":{"date-parts":[[2021,3,29]],"date-time":"2021-03-29T01:57:58Z","timestamp":1616983078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":99,"title":["Emerging Therapeutics for Immune Tolerance: Tolerogenic Vaccines, T cell Therapy, and IL-2 Therapy"],"prefix":"10.3389","volume":"12","author":[{"given":"Cody D.","family":"Moorman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue J.","family":"Sohn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyewon","family":"Phee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,29]]},"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":"10.1101\/cshperspect.a006908","article-title":"Historical overview of immunological tolerance","volume":"4","author":"Schwartz","year":"2012","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1600-065X.2011.01019.x","article-title":"Mechanisms of tolerance","volume":"241","author":"Bluestone","year":"2011","journal-title":"Immunol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12395","article-title":"Human autoimmune diseases: a comprehensive update","volume":"278","author":"Wang","year":"2015","journal-title":"J Intern Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2011.01016.x","article-title":"Immune tolerance in multiple sclerosis","volume":"241","author":"Goverman","year":"2011","journal-title":"Immunol Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2017.02.006","article-title":"Immunopathogenesis of Rheumatoid Arthritis","volume":"46","author":"Firestein","year":"2017","journal-title":"Immunity"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032713-120225","article-title":"Immunology of psoriasis","volume":"32","author":"Lowes","year":"2014","journal-title":"Annu Rev Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007807","article-title":"Breakdown in peripheral tolerance in type 1 diabetes in mice and humans","volume":"2","author":"Jeker","year":"2012","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1090051","article-title":"Anti-TNF therapy, from rationale to standard of care: what lessons has it taught us","volume":"185","author":"Feldmann","year":"2010","journal-title":"J Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/intimm\/dxv063","article-title":"Therapeutic antibodies that target inflammatory cytokines in autoimmune diseases","volume":"28","author":"Lai","year":"2015","journal-title":"Int Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00460","article-title":"Drugs for Autoimmune Inflammatory Diseases: From Small Molecule Compounds to Anti-TNF Biologics","volume":"8","author":"Li","year":"2017","journal-title":"Front Pharmacol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1111\/exd.12265","article-title":"Jakpot! 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