Volume 13 Issue 12, December 2012

Autoinflammation and immunodeficiency are rare in humans, but the rate of discovery of these conditions has increased. Three patients have now been characterized in whom deficiency in HOIL-1, a component of the LUBAC complex, leads to these conditions.

Diseased host cells are eliminated more effectively when natural killer cells grow up in the presence of classical major histocompatibility complex (MHC) class I molecules. The nonclassical MHC class I molecule H2-M3 can exert an analogous effect.

Bacterial cyclic dinucleotides are recognized by the innate immune system, and this leads to the induction of type I interferons. The mammalian helicase DDX41 directly binds cyclic dinucleotides and mediates the signaling pathway to the induction of type I interferons.

Mathematical modeling shows that two members of the NF-κB family of transcription factors, RelB and p50, form heterodimers and participate in the canonical NF-κB pathway in dendritic cells.

Interleukin 2 (IL-2) and IL-15 use receptors with the same signaling subunits. New structural data show that the signaling complexes they form are topologically nearly identical, which suggests that other factors are responsible for the distinct signaling properties of these complexes.

Activation of type I interferon by c-di-GMP and c-di-AMP depends on the adaptor STING. Cheng and colleagues show that these bacterial secondary messengers are detected by the helicase DDX41, which forms a complex with STING.

Noncanonical RelB–NF-κB2 heterodimers function in homeostatic signaling. Hoffmann and colleagues show that RelB-p50 complexes, regulated by IκB, exist in dendritic cells and contribute to inflammatory gene expression via canonical NF-κB pathway activation.

NK cell licensing is governed by the interaction of Ly49 receptors with peptide-MHC complexes. Smyth and colleagues show that the nonclassical MHC class I molecule H2-M3 can also license NK cell functional development.

The linear ubiquitination complex (LUBAC) is poorly understood in humans. Casanova and colleagues identify natural mutations in a component of human LUBAC and use this to dissect its function in vivo and in vitro.

The receptors for IL-2 and IL-15 share many characteristics, but mice deficient in either receptor have very different phenotypes. Garcia and colleagues present the quaternary structure of the complex of IL-15 and its receptor, as well as insights into its unique signaling properties.

Lineage development is accompanied by specification of gene expression. Murre and colleagues show that during B cell development, many genes relocate in the nucleus, driven by chromatin-looping interactions with transcription factors.

The Igh locus undergoes a precise order of gene rearrangement during V(D)J recombination. Sen and colleagues show the recruitment of the RAG recombinase is confined to DJH junctions by highly localized epigenetic modifications.

The complement receptor CD46 and the Notch-Jagged system are important for the differentiation of helper T cells. Kemper and colleagues demonstrate that Jagged1 is a physiological ligand for CD46 and is critical for the generation of T helper type 1 cells in humans.