Reviews & Analysis

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.

Innate immune responses need to be tightly controlled to avoid autoimmune and inflammatory diseases. The atypical orphan nuclear receptor SHP has now been identified as a negative regulator of Toll-like receptor–induced activation of the transcription factor NF-κB.

The generation of Ly6C⁻ patrolling monocytes requires the transcription factor NR4A1 (Nur77). This finding provides insight into the development and function of these blood-resident cells.

Systems biology has emerged as a promising research strategy that can be applied to vaccine development. This approach can lead to the identification of new mechanisms and predictors of inactivated vaccine immunogenicity.

New data show that the interferon-induced gene product IFIT1 is a sensor for 5′-triphosphorylated RNA of viral origin and that it functions within a larger IFIT complex to inhibit viral replication.

The T cell antigen receptor is functionally coupled to many kinases and adaptor proteins. Analysis of the spatiotemporal organization of the T cell antigen receptor signaling cascade suggests that adaptor-containing intracellular vesicles are essential for proper signal propagation.

Although the role of adaptive immunity in asthma is well characterized, there is relatively little understanding of the contribution of innate immunity to asthma. Studies now suggest that interleukin 13 produced by innate natural helper cells in the lungs has a substantial and underappreciated role in asthma exacerbation.

In response to inhaled pathogens, lymphoid tissues can form in the lung. The driving force behind this organogenic process turns out to be interleukin 17–mediated activation of lung stromal cells.

The transcription factor Foxp1 helps maintain the quiescence of naive T cells by inhibiting IL-7Rα expression and diminishing signaling by the kinase Erk.

The transcription factor BATF directly regulates key components of the formation and function of follicular helper T cells and antibody class switching in B cells.

Identification of the pathogenic cytokines that underlie the IL-23-dependent disease progression of experimental autoimmune encephalomyelitis has proven elusive. Evidence now points to GM-CSF.

B cell generation is disturbed in four newly identified mouse mutants bearing X-linked mutations in the gene encoding the ATPase ATP11C. These findings suggest that the distribution of membrane phospholipids confers a yet-to-be delineated developmental signal.

The interaction between hematopoietic stem cells and their niche is critical for the lifelong maintenance of the blood system. New research shows that crosstalk between stromal components of the niche mediates secretion of the chemokine CXCL12.

The inflammasome has been linked to metabolic disorders such as obesity and type 2 diabetes. Data now suggest that the crosstalk between the inflammasome and autophagy critically mediates cytoplasmic receptor NLRP3–dependent activation of the inflammasome by the saturated fatty acids contained in a high-fat diet.

In addition to their classical function in antigen presentation and their lesser known ability to act as signal transducers, major histocompatibility complex class II molecules are now shown to promote Toll-like receptor signaling. This intriguing role requires intracellular association with the kinase Btk and the costimulatory molecule CD40.

The development and function of TCRαβ⁺CD8αα⁺ intraepithelial lymphocytes remain poorly understood. These cells are now shown to require transforming growth factor-β for development and proper expression of characteristic surface homodimers of CD8α.

Analysis of the serine-threonine phosphoproteome leads to the intriguing find that phosphorylation of the histone deacetylase HDAC7 is key to cytotoxic T lymphocyte function.

Regulatory T cells adopt specialized differentiation programs controlled by transcription factors. The transcription factors Blimp-1 and IRF4 are now shown to be pivotal in the maturation of effector regulatory T cells.

Helminth parasites are adept at dampening immunity. New data showing that intracellular degradative pathways are manipulated have important implications for therapy.

The NADPH oxidase of professional phagocytes has an important role in host defense against certain microbes, including tuberculous mycobacteria. The identification of patients with rare inherited hypomorphic mutations in genes encoding components of this enzyme complex could produce new mechanistic insights.