Volume 18 Issue 1, January 2017

The relationship between atopic dermatitis and air pollution has been long debated but has now been connected via the aryl hydrocarbon receptor and its control of skin innervation and the consequent triggering of an itch-scratch response.

The deubiquitinase USP15 acts with the ubiquitin ligase TRIM25 to activate a type I interferon response and exacerbate microbial and autoimmune neuroinflammation.

Different cellular sources and signaling mechanisms mediate the effects of IL-6 on the generation of pathogenic T_H17 helper T cells and the suppression of Foxp3⁺ regulatory T cells.

Altered signaling via the T cell antigen receptor (TCR) promotes an adipose-tissue-like phenotype in invariant natural killer cells (iNKT cells) during thymic development and causes selective enrichment for iNKT cells in adipose tissues.

A surprising molecular mechanism underlying signal integration and programmed proliferation in adaptive immunity has been identified: the cell-cycle regulator Myc enables a lymphocyte to add up the strength of signals it receives and time its response accordingly.

Natural killer cells are a rapid source of the cytokine IFN-γ that influences ensuing immune responses. Schwab and colleagues report that gradients of the signaling lipid S1P regulate the positioning of natural killer cells in lymph nodes necessary for this response.

The signaling adaptor TRAF1 is involved in TNFR-induced survival. Watts and colleagues demonstrate that TRAF1 also negatively regulates NF-κB activation by interfering with linear ubiquitination of the signaling subunit NEMO.

Sant’Angelo and colleagues show that disruption of a hydrophobic patch in the T cell antigen receptor on natural killer T cells alters their development, which results in the selective accumulation of adipose-tissue-specific natural killer T cells.

TET proteins regulate 5-methylcytosine epigenetic marks, and thereby regulate chromatin accessibility. Rao and colleagues show that the combined loss of TET2 and TET3 in thymocytes skews development to iNKT17 cells as a result of upregulation of RORγt, which leads to lymphoproliferative disease and premature death.

Cerebral malaria infection can provoke fatal neuroinflammation. Gros and colleagues identify an ubiquitin-modification axis that exacerbates neuroinflammation and that involves TRIM25 and USP15, which jointly promote type I interferon production.

There are suspected links between air pollution and atopic dermatitis, but the mechanism has remained unclear. Yamamoto and colleagues demonstrate that air pollutants trigger activation of the aryl hydrocarbon receptor in the skin, hyperinnervation and an itch-scratch cycle that leads to atopic dermatitis.

Korn and colleagues report that Sirpα⁺ dendritic cells trans-present the cytokine IL-6 to T cells through a process that requires its receptor IL-6Rα bound to dendritic cells and that trans-presentation is needed to generate pathogenic cells of the T_H17 subset of helper T cells in vivo.

Lillemeier and colleagues describe a cycle of recruitment, activation and release of Zap70 kinase at phosphorylated T cell antigen receptors. According to this model, the receptor acts as a ‘catalytic unit’ that amplifies antigenic stimuli.

Lymphocytes integrate multiple input signals to regulate the extent of their proliferative response. Hodgkin and colleagues demonstrate that the proto-oncoprotein Myc is a cell-intrinsic division timer.

Krönke and colleagues show that the cytokine IL-23 controls the glycosylation profile and inflammatory activity of autoantibodies through control of sialyltransferase activity in plasma cells mediated by the T_H17 subset of helper T cells.