Oral tolerance: therapeutic implications for autoimmune diseases

Area of Science:

• Immunology
• Gastroenterology

Background:

• Oral tolerance is the immune system's suppression of responses to orally administered antigens.
• It involves various mechanisms, including active suppression, clonal anergy, and deletion, influenced by antigen dose.

Purpose of the Study:

• To explore the mechanisms and therapeutic potential of oral tolerance.
• To review its effectiveness in animal models and human trials for autoimmune and inflammatory diseases.

Main Methods:

• Induction of oral tolerance involves specific regulatory T cell subsets (Th2, Th3, CD4+CD25+, LAP+).
• Enhancement factors include cytokines (IL-4, IL-10, TGF-beta), adjuvants (CTB), and continuous antigen feeding.
• Nasal tolerance is also discussed as an alternative with lower dose requirements.

Main Results:

• Oral and nasal tolerance successfully suppressed various animal models of autoimmune diseases (e.g., EAE, arthritis, diabetes) and non-autoimmune conditions (e.g., asthma, atherosclerosis).
• Human trials for autoimmune diseases (MS, arthritis, diabetes) and allergies have shown positive results, with ongoing trials for arthritis, MS, and diabetes.

Conclusions:

• Mucosal tolerance offers a non-toxic, easily administered, and antigen-specific treatment strategy for inflammatory and autoimmune conditions.
• Successful human application hinges on optimizing dose, immune markers, route, formulation, adjuvants, combination therapy, and early intervention.