Volume 12 Issue 12, December 2011

Two studies identify a tissue-autonomous innate immune mechanism whereby infection provokes epithelial cells to produce IL-17C that engages an epithelial receptor composed of IL-17RA and IL-17RE chains, which promotes host defense and immune activation.

Improper termination of inflammatory signals can contribute to tumorigenesis. Cyld and Itch form an ubiquitin-editing complex that cooperatively downregulates the kinase Tak1 and thereby attenuates downstream activation of the transcription factor NF-κB.

Natural killer T cells (NKT cells) recognize lipid-based antigens presented by CD1d. The mammalian glycolipid β-glucosylceramide, a ubiquitous self antigen for NKT cells, is upregulated by microbial danger signals, which leads to activation of NKT cells in the absence of foreign glycolipid antigen.

Becoming covered in platelets rescues complement-opsonized blood-borne bacteria from rapid clearance by macrophages and redirects them to dendritic cells. Although this allows priming of T cells and the generation of immune memory, bacteria can exploit this route as a beachhead and disseminate throughout host tissues.

The transcription factor STAT5 can activate or repress gene expression depending on whether binding of dimer or tetrameric STAT5 occurs. Tetrameric STAT5 recruits the chromatin modifier Ezh2 to silence gene expression.

IL-17RE is an orphan receptor of the IL-17 receptor family. Qian and colleagues identify IL-17RE as the receptor specific for IL-17C signaling in mucosal defense against intestinal pathogens.

IL-17C is induced in epithelia by bacterial and inflammation stimuli. Pappu and colleagues show that IL-17C signals in an autocrine manner through the IL-17RA-IL-17RE receptor complex to regulate epithelial immune responses.

The stability of interleukin 6 transcripts is negatively regulated by the RNAse regnase-1. Akira and colleagues show that regnase-1 is targeted for degradation by phosphorylation mediated by the kinase IKK, which allows more interleukin 6 production.

Signaling by the inflammatory cytokine TNF is tightly regulated. Venuprasad and colleagues show that ubiquitin modification of the kinase TAK1 by Itch and Cyld terminates TNF signaling.

The deubiquitinase A20 is a negative regulator of transcription factor NF-κB signaling pathways. Ma and colleagues show that mice lacking A20 expression in dendritic cells have defective lymphocyte homeostasis and develop spontaneous inflammatory disease.

The priming of an antibacterial response requires the uptake and presentation of bacterial antigens by dendritic cells. Busch and colleagues describe a new platelet-dependent mechanism for shuttling bacteria to dendritic cells.

The identification of an endogenous ligand for natural killer T cells has remained elusive. Brenner and colleagues identify β-d-glucopyranosylceramide as a physiologically important self ligand for these cells.

The transcription factor STAT5 commonly activates gene transcription. Clark and colleagues show that tetrameric STAT5, induced by high concentrations of interleukin 7, can repress gene expression by recruitment of the histone methyltransferase Ezh2.

Id proteins negatively regulate the binding of E-protein transcription factors to DNA. Goldrath et al. show that Id2 and Id3 are important in the generation of memory in distinct functional populations of CD8⁺ cells.

The molecular basis of CD8⁺ memory is still being delineated. Gattinoni et al. show that the DNA-binding inhibitor Id3 is critical for the formation of long-lived memory.

The T_H17 subset of helper T cells can produce interleukins IL-17 and IL-22, although regulation of these cytokines expression differ. Ouyang and colleagues show that TGF-β induces upregulation of the transcription factor c-Maf, which suppresses IL-22 expression.