Volume 12 Issue 9, September 2011

In addition to its recognized function as an enzyme that catalyzes tryptophan, indoleamine 2,3-dioxygenase (IDO) acts as an intracellular signal transducer, in response to transforming growth factor-β (TGF-β), to induce a stably regulatory phenotype in plasmacytoid dendritic cells.

Tuberins, the tumor-suppressor proteins that regulate signaling via the kinase mTOR, now emerge as essential enforcers of T cell quiescence that promote survival.

Proinflammatory signaling by the interleukin 17 receptor requires the adaptor Act1. Two studies identify an additional function for Act1 and identify new participants that regulate the inflammatory effects of IL-17.

The kinase IKKα has a well-described activating role in the noncanonical transcription factor NF-κB pathway. Evidence now suggests that IKKα also inhibits the canonical NF-κB pathway by phosphorylating the scaffold protein TAX1BP1 to promote the assembly of the A20 ubiquitin-editing complex.

In contrast to microbial natural killer T cell ligands, self glycolipid antigens are β-linked. Rossjohn and co-workers provide the mechanism for the autoreactivity of natural killer T cell antigen receptors toward β-glycosylated agonists.

The deubiquitinase A20 limits excessive cytokine expression by shutting down activation of the transcription factor NF-κB. Harhaj and colleagues show that the kinase IKKα activates the A20 ubiquitin-editing complex by phosphorylating the regulatory molecule TAX1BP1.

The adaptor Act1 links the interleukin 17 receptor to downstream signaling pathways. Li and colleagues show that phosphorylation of Act1 by the kinase IKKi is necessary for recruitment of the adaptors TRAF2 and TRAF5 and activation of the pathway of mitogen-activated protein kinases.

Interleukin 17 promotes antibacterial and antifungal immune defenses. Hamilton and colleagues show that it induces complexes of the adaptors Act1 and TRAF2 or TRAF5 that inhibit the mRNA-destabilizing action of the splicing factor SF2 (ASF), thereby prolonging the half-life of chemokine and cytokine mRNAs.

MicroRNAs contribute to post-transcriptional controls that fine-tune protein expression. Cao and colleagues identify the microRNA miR-29 as a regulator of the expression of interferon-γ protein and show that intracellular infection with pathogens dampens miR-29 expression.

The tryptophan-catalytic activity of IDO in dendritic cells is known to regulate immune responses. Grohmann and co-workers show that IDO also functions as an intracellular signal transducer in response to transforming growth factor-β.

Lymphatic vessels provide conduits that channel leukocytes to draining lymph nodes. Förster and colleagues show that lymph-derived dendritic cells and T cells take different paths to enter draining lymph nodes.

Immune quiescence is sustained through a tightly regulated but poorly understood process. Chi and colleagues show that the tumor suppressor Tsc1 is essential in maintaining T cell quiescence.

The DNA-binding factor SATB1 is known as a chromatin organizer. Schultze and colleagues show regulation of SATB1 expression by the transcription factor Foxp3 is necessary to confer suppression of effector cell activity.

The generation of CD8⁺ T cell memory requires both CD4⁺ T cells and dendritic cells. Schoenberger et al. show that autocrine production of interleukin 2 by licensed CD8⁺ T cells is also crucial.