Oral Tolerance: Therapeutic Implications for Autoimmune Diseases
Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral...
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Wiley
2006-01-01
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| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1080/17402520600876804 |
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| author | Ana M. C. Faria Howard L. Weiner |
| author_facet | Ana M. C. Faria Howard L. Weiner |
| author_sort | Ana M. C. Faria |
| collection | DOAJ |
| description | Oral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy. |
| format | Article |
| id | doaj-art-3ffa27f1aea14e22b7166af2fbc03e36 |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2006-01-01 |
| publisher | Wiley |
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| series | Clinical and Developmental Immunology |
| spelling | doaj-art-3ffa27f1aea14e22b7166af2fbc03e362025-08-20T03:55:36ZengWileyClinical and Developmental Immunology1740-25221740-25302006-01-01132-414315710.1080/17402520600876804Oral Tolerance: Therapeutic Implications for Autoimmune DiseasesAna M. C. Faria0Howard L. Weiner1Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, BrazilHarvard Medical School, Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, MA, USAOral tolerance is classically defined as the suppression of immune responses to antigens (Ag) that have been administered previously by the oral route. Multiple mechanisms of tolerance are induced by oral Ag. Low doses favor active suppression, whereas higher doses favor clonal anergy/deletion. Oral Ag induces Th2 (IL-4/IL-10) and Th3 (TGF-β) regulatory T cells (Tregs) plus CD4+CD25+ regulatory cells and LAP+T cells. Induction of oral tolerance is enhanced by IL-4, IL-10, anti-IL-12, TGF-β, cholera toxin B subunit (CTB), Flt-3 ligand, anti-CD40 ligand and continuous feeding of Ag. In addition to oral tolerance, nasal tolerance has also been shown to be effective in suppressing inflammatory conditions with the advantage of a lower dose requirement. Oral and nasal tolerance suppress several animal models of autoimmune diseases including experimental allergic encephalomyelitis (EAE), uveitis, thyroiditis, myasthenia, arthritis and diabetes in the nonobese diabetic (NOD) mouse, plus non-autoimmune diseases such as asthma, atherosclerosis, colitis and stroke. Oral tolerance has been tested in human autoimmune diseases including MS, arthritis, uveitis and diabetes and in allergy, contact sensitivity to DNCB, nickel allergy. Positive results have been observed in phase II trials and new trials for arthritis, MS and diabetes are underway. Mucosal tolerance is an attractive approach for treatment of autoimmune and inflammatory diseases because of lack of toxicity, ease of administration over time and Ag-specific mechanism of action. The successful application of oral tolerance for the treatment of human diseases will depend on dose, developing immune markers to assess immunologic effects, route (nasal versus oral), formulation, mucosal adjuvants, combination therapy and early therapy.http://dx.doi.org/10.1080/17402520600876804 |
| spellingShingle | Ana M. C. Faria Howard L. Weiner Oral Tolerance: Therapeutic Implications for Autoimmune Diseases Clinical and Developmental Immunology |
| title | Oral Tolerance: Therapeutic Implications for Autoimmune Diseases |
| title_full | Oral Tolerance: Therapeutic Implications for Autoimmune Diseases |
| title_fullStr | Oral Tolerance: Therapeutic Implications for Autoimmune Diseases |
| title_full_unstemmed | Oral Tolerance: Therapeutic Implications for Autoimmune Diseases |
| title_short | Oral Tolerance: Therapeutic Implications for Autoimmune Diseases |
| title_sort | oral tolerance therapeutic implications for autoimmune diseases |
| url | http://dx.doi.org/10.1080/17402520600876804 |
| work_keys_str_mv | AT anamcfaria oraltolerancetherapeuticimplicationsforautoimmunediseases AT howardlweiner oraltolerancetherapeuticimplicationsforautoimmunediseases |