Gut immune system and oral tolerance

Abstract

Gut mucosal surfaces separate the external environment from the internal sterile environment and so represent a first line of defence system. This barrier faces environments rich in pathogens that have developed effective mechanisms for colonisation of epithelial surfaces and invasion of mucosal tissues, but also harmless antigens such as food, airborne antigens or commensal bacterial flora. The latter represent the vast majority of the encountered antigens and require an appropriate response characterised by either ignorance or active suppression. However, for the former, a robust immune response is needed. Mucosae have developed a complex immune system that is capable of mounting an immune response against pathogenic antigens, while maintaining the required ignorance or active suppression against non-pathogenic antigens. Taking advantage of this knowledge, strategies have been devised to induce oral tolerance to antigens involved in experimental autoimmune disease or human conditions. It is now known that oral tolerance induces the up-regulation and activation of T cells with regulatory properties, a subtype of CD4⁺ T cells whose function is to regulate functions of other T lymphocytes to avoid excessive immune activation. Amongst them, the Th3 cells (cells that express the latency-associated peptide on the surface and secrete transforming growth factor β, a cytokine with immunoregulatory properties) are especially relevant in the induction of oral tolerance. Orally fed antigens seek to generate these types of cells in the treatment of autoimmune diseases in experimental animals or human subjects.