The contribution of NF-κB signalling to immune regulation and tolerance.

Abstract

Immune regulation is necessary to control inflammatory responses and to prevent autoimmune diseases. Therefore, mechanisms of central and peripheral tolerance have evolved to ensure that T cells recognize antigens as self- or non-self-antigens. The thymus is crucially important for central tolerance induction to self-antigens via negative selection of T cells. However, if T cells escape negative selection in the thymus and enter the periphery, peripheral mechanisms are active to warrant immune tolerance. Secondary lymphoid organs, as well as tolerogenic dendritic cells and regulatory T cells, play an important role in peripheral tolerance. In chronic inflammatory diseases, tertiary lymphoid organs are sometimes formed that may also be involved in the induction of peripheral tolerance. This review discusses the main processes that are involved in immune regulation and tolerance, and focuses on the contribution of NF-κB signalling to these processes. This narrative review is based on peer-reviewed publications listed on PubMed up to December 2014. The focus of our literature search was on studies investigating the role of (non)canonical NF-κB signalling in central and peripheral mechanisms of tolerance. Only studies published in English language were considered. This review discusses the immune phenotype of mutant mice with defective (non)canonical NF-κB signalling, corroborated with human data, and emphasizes the contribution of the noncanonical NF-κB pathway to immune regulation and tolerance induction. Noncanonical NF-κB signalling has an important immunoregulatory role in the immune system and contributes to both central and peripheral mechanisms of tolerance.