Volume 13 Issue 4, April 2012

Type 1 diabetes is usually diagnosed after most insulin-producing islets of Langerhans have already been destroyed. However, magnetic resonance imaging can be used to predict the onset of type 1 diabetes, and a benign prognosis correlates with the presence of anti-inflammatory tissue-resident macrophages.

After class switching in naive B cells, memory B cells and plasma cells that produce immunoglobulin E (IgE⁺ cells) develop through a germinal-center IgE⁺ intermediate cell without an IgG1 phase. In addition, cellular IgE memory resides in IgE⁺ memory B cells, and IgG1⁺ memory B cells are not an important source of IgE memory.

The multiprotein inflammasome complexes are important in responses to microbes but are also increasingly recognized as having key pathogenic roles in a variety of diseases from cancer to obesity.

Nearly a decade ago, the concept of inflammasomes was introduced. Since then, the biochemical characterization of the inflammasomes has led to a richer understanding of innate immune responses in the context of infection and sterile inflammation. This has provided the rationale for successful clinical therapies for a spectrum of hereditary periodic fever syndromes and potentially for some metabolic pathologies.

Magnetic resonance imaging of magnetic nanoparticles allows monitoring of disease progression in type 1 diabetes. Mathis and colleagues use this approach to predict diabetes onset and identify a pathway important in the regulation of disease progression.

Deficiency in the kinase Btk results in X-linked agammaglobulinemia in humans. Morio and colleagues show that Btk confines the adaptor Mal in the cytoplasm in neutrophils to prevent excessive generation of reactive oxygen species, thereby prolonging neutrophil longevity.

Endotoxin tolerance dampens responses to subsequent Toll-like receptor stimulation, but the molecular details of this process are still being defined. Wei and colleagues show that endotoxin tolerance requires degradation of the coactivator RIP140.

Cytoplasmic nucleic acids induce interferon responses via a pathway dependent on the kinase TBK1 and transcription factor IRF3. Wang and colleagues show that the receptor NLRP4 limits this response by recruiting the ubiquitin ligase DTX4 to target TBK1 for proteasomal degradation.

The origin of immunoglobulin E–producing (IgE⁺) B cells has been controversial. Wu and colleagues demonstrate that IgE⁺ B cells develop in a conventional way in germinal centers and give rise directly to IgE⁺ memory cells.

T_H1 and T_FH cells are associated with the transcription factors T-bet and Bcl-6, respectively. Weinmann and colleagues show that IL-2 signaling influences the Bcl-6/T-bet ratio that governs effector cell fate.

The commitment stage at which progenitors seed the thymus remains unclear. Jacobsen and colleagues show that the earliest progenitors in the neonatal thymus have combined myeloid, T lymphocyte and B lymphocyte potential but not megakaryocyte-erythroid potential.

A comprehensive overview, and four review articles examine activation, regulation and function of the inflammasome.