NF-κB in control of regulatory T cell development, identity, and function

Regulatory T cells (Treg cells) act as a major rheostat regulating the strength of immune responses, enabling tolerance of harmless foreign antigens, and preventing the development of pathogenic immune responses in various disease settings such as cancer and autoimmunity. Treg cells are present in all lymphoid and non-lymphoid tissues, and the latter often fulfill important tasks required for the physiology of their host organ. The activation of NF-κB transcription factors is a central pathway for the reprogramming of gene expression in response to inflammatory but also homeostatic cues. Genetic mouse models have revealed essential functions for NF-κB transcription factors in modulating Treg development and function, with some of these mechanistic insights confirmed by recent studies analyzing Treg cells from patients harboring point mutations in the genes encoding NF-κB proteins. Molecular insights into the NF-κB pathway in Treg cells hold substantial promise for novel therapeutic strategies to manipulate dysfunctional or inadequate cell numbers of immunosuppressive Treg cells in autoimmunity or cancer. Here, we provide an overview of the manifold roles that NF-κB factors exert in Treg cells.