Volume 13 Issue 11, November 2012

The kinase TBK1 participates in signaling pathways that induce antimicrobial responses. TBK1 is also necessary for the suppression of excessive production of immunoglobulin A by accelerating destruction of the kinase NIK.

A fundamental mystery of the biology of germinal center B cells is why it seems that these rapidly dividing B cells lack expression of c-Myc, a transcriptional regulator intimately linked to cell metabolism and proliferation. This mystery has now been resolved.

Limiting immune responses is critical for protecting the host from harm. The p110δ isoform of the kinase PI(3)K acts as a balance between pro- and anti-inflammatory TLR4 signaling in dendritic cells.

The deubiquitinating enzyme USP25 restricts ubiquitination of the adaptors TRAF5 and TRAF6 and signaling via interleukin 17 and thus joins several ubiquitin-modifying enzymes already known to regulate this biomedically important pathway.

TLR4 signaling shifts from plasma membrane TIRAP-MyD88–mediated pathways to endosomal TRAM-TRIF–mediated signaling. Vanhaesebroeck and colleagues show that the kinase PI(3)K p110δ is required for TLR4 internalization and degradation of TIRAP.

Signaling through toll-like receptors induces cytokines and type I interferon. Moynagh and colleagues show that the E3 ubiquitin ligase Pellino3 specifically represses the expression of type I interferon in response to TLR3 activation.

Successful pathogens can overcome innate immune defenses. Ge and colleagues show that Tir protein expressed by enteropathogenic Escherichia coli is injected into host cells, where it interferes with adaptor TRAF6–dependent signaling.

Hematopoietic stem cells must be shielded from toxic and inflammatory insults to ensure lifelong blood cell production. Lapidot and colleagues identify a rare bone marrow macrophage population that protects hematopoietic stem cells.

The molecular control of germinal center selection is still being determined. Dalla-Favera and colleagues show that the cell-cycle regulator c-Myc is essential for B cell selection and reentry into the germinal center.

The regulator c-Myc is well known for controlling cell growth but, paradoxically, evidence for its involvement in germinal centers has proven elusive. Rajewsky and colleagues show that it is essential for their development and maintenance.

How isotype-specific immunoglobulin production is regulated is largely unknown. Sun and colleagues show that the kinase TBK1 acts as a negative regulator of IgA class switching by attenuating NIK-mediated NF-κB signaling.

How IL-17 signaling is regulated remains poorly understood. Dong and colleagues identify the ubiquitin-specific protease USP25 as a negative regulator of IL-17-mediated signaling and inflammation.

By comparing gene-expression profiles, Randolph and colleagues distinguish different types of macrophages and pinpoint the differences between macrophages and dendritic cells.