Volume 15 Issue 6, June 2014

Non-coding RNA accounts for a large proportion of the mammalian genome. In this Focus Review, Martin Turner and colleagues explore how these RNA species regulate gene transcription in the immune system.

RNA-binding proteins regulate gene expression by interacting with mRNA and destabilizing it. In this Focus Review, Kontoyiannis and colleagues describe how this class of protein affects various aspects of immunological function.

Translation of mRNA is controlled by a whole host of tightly regulated processes. In this Focus Review, Piccirillo et al. describe how translational skewing can serve a key role in the immune system.

Immune system proteins are subject to numerous post-translational modifications. In this Focus Review, Mowen and David describe the key 'non-conventional' modifications such as acetylation and nitrosylation that affect immunologically-relevant proteins.

Approximately 10% of the human genome is involved in either ubiquitination or phosphorylation. In this Focus Review, Cohen describes the mutations underlying the diseases afflicting these important post-translational systems.

Natural killer (NK) cells are innate lymphocytes that exhibit many features of adaptive immunity, such as long-lived memory. This can now be extended to the transcriptional circuits that control the proliferation of NK cells and lymphocytes.

The colonization of the colon with commensal microflora drives the induction and population expansion of regulatory T cells, an immunological adaption needed to prevent mucosal inflammation. The epigenetic modifier Uhrf1 acts as a key molecular mediator of such expansion and the establishment of a harmonious mucosal environment.

The DNA-damage sensor Rad50 couples the sensing of cytosolic DNA to the innate immunological adaptor CARD9 to stimulate DNA-dependent activation of the transcription factor NF-κB. This facilitates DNA virus–stimulated production of the cytokine IL-1β.

Double-stranded DNA (dsDNA) in the cytoplasm triggers IL-1β production as an antiviral response. Ruland and colleagues describe the formation of dsDNA-Rad50-CARD9 signaling complexes for NF-κB activation and the generation of pro-IL-1β after infection with a DNA virus.

Natural killer (NK) cells help control viral infections and mediate antitumor responses. Joseph Sun and colleagues show the transcription factor Zbtb32 antagonizes Blimp-1 to mediate replicative bursts of NK cells.

Double-positive αβ thymocytes undergo negative selection on thymic epithelial cells. Ziegler and colleagues show that TGF-β limits numbers and function of medullary thymic epithelial cells, thus influencing the resultant T cell repertoire.

Sun and colleagues show that the deubiquitinase USP15 stabilizes expression of the E3 ubiquitin ligase MDM2 in T cells, which results in inhibition of T cell activation, and in cancer cells, which results in survival of cancer cells.

Regulatory T cells proliferate robustly in gut lymphoid tissues. Hase et al. show that this proliferation requires their expression of the epigenetic regulator Uhrf1, which is increased in response to IL-2 produced by effector T cells.

The transcription factor Foxp3 is essential for the function of regulatory T cells (T_reg cells). Rudensky and colleagues show binding of Foxp3 poises target genes for repression and, after activation of T_reg cells, recruits the histone methyltransferase Ezh2.

A series of Reviews specially commissioned by Nature Immunologydiscuss post-transcriptional and post-translational modifications in the immune system. The Focus covers the role of such modifications in various aspects of the immune system ranging from development to activation to immunopathology.