Volume 14 Issue 1, January 2013

The mechanisms by which cells detect and fight foreign organisms is crucial for the host defense against infection. The sensing of cytosolic DNA is pivotal in this process, is kept in check by the exonuclease Trex1 and has been linked to lysosomal biogenesis via the transcription factor TFEB in an interferon-independent manner.

Feedback inhibition by interferon-γ blocks the NLRP3 inflammasome by triggering inducible nitric oxide synthase (iNOS), and the resulting nitric oxide (NO) thio-nitrosylates NLRP3, shutting it down. This prevents excessive immunopathology during chronic infection with Mycobacterium tuberculosis.

During sterile inflammation, emigrating leukocytes sequentially engage subsets of pericytes associated with blood vessels and acquire adhesive, migratory and survival signals.

Psoriasis is associated with the T_H17 subset of helper T cells. Dysregulation of interleukin 17 (IL-17) signaling leads to enhanced T_H17 differentiation, more production of IL-22 and IL-22-dependent skin inflammation.

ARIH2 is a RING-between-RING E3 ligase. Pellegrini and colleagues show that ARIH2 is needed to limit excessive NF-κB signaling in DCs. Loss of ARIH2 is associated with embryonic death due to excessive inflammatory responses.

Modulation of integrin activation can contribute to regulation of inflammation. Arase and colleagues demonstrate that PILRα, an ITIM-containing inhibitory receptor, negatively regulates integrin activation and neutrophil infiltration during inflammation.

The signals involved in coordinating the navigation of myeloid cells in tissues are incompletely understood. Massberg and colleagues show that NG2⁺ pericytes control the pattern and efficacy of interstitial leukocyte migration.

Chronic infections can result in harmful production of the proinflammatory cytokine IL-1 generated via the NLRP3 inflammasome. Sassetti et al. demonstrate that IL-1 activated by Mycobacteria results in nitrosylation and consequent regulation of the NLRP3 inflammasome.

Trex1 is a cytosolic exonuclease that limits sensing of intracellular DNA. Yan and colleagues show that Trex1 deficiency spontaneously heightens adaptor STING–dependent proinflammatory responses via a pathway involving regulation of lysosomal biogenesis.

Psoriasis is associated with heightened T_H17 responses. Li and colleagues show that the IL-17R signaling adaptor Act1 requires the chaperone protein hsp90. Defective signaling leads to exuberant IL-22 production and enhanced disease.

Gaus and colleagues show that the conformational states of the tyrosine kinase Lck intrinsically control its distribution and clustering at the plasma membrane.

Using the Immunological Genome compendium, Brenner and colleagues shed light on the transcriptional programs that operate during the course of iNKT cell development and in peripheral CD4⁺ and CD4^– iNKT cell subsets.