Volume 15 Issue 4, April 2014

The PYRIN domain–only protein POP3 sets limits for activation of the AIM2 inflammasome after cytosolic double-stranded DNA is sensed.

Innate lymphoid cells, marginal reticular cells and B cell–helper neutrophils interact to promote antibody secretion by B cells in the marginal zone of the spleen in humans and mice.

The activation of dendritic cells by Toll-like receptors leads to a rapid enhancement in glycolysis. Glucose is metabolized to pyruvate and from there to citrate in the mitochondria, which leads ultimately to membrane biosynthesis in the endoplasmic reticulum and Golgi to support the activation of dendritic cells.

Functional coupling of receptors for immunoglobulin G (FcγRI) and interferon-γ (IFN-γR) generates a context-dependent signaling pathway in macrophages.

Recent findings in the SIV-monkey model provide new evidence that stimulating effective CD8⁺ T cell immunity could provide protection. McMichael and Koff explore the path forward for optimizing such responses in humans.

Activation of dendritic cells induces a metabolic switch from oxidative phosphorylation to glycolysis. Pearce and colleagues show TLR signaling rapidly induces glycolysis by activating a TBK1–IKKε–Akt–HK-II kinase cascade to support the fatty acid synthesis required for the activation of dendritic cells.

How the generation of outcomes specific to external cues is achieved by a small number of signal-transduction pathways remains unclear. Medzhitov and colleagues describe a mechanism for signal integration based on coupling of the ITAM and Jak-STAT signaling pathways.

Much is known about the activation of inflammasomes, but less is known about their negative regulation. Stehlik and colleagues demonstrate that the pyrin domain–only protein POP3 negatively regulates inflammasomes involved in sensing DNA.

Marginal zone B cells provide rapid antibody responses to blood-borne antigens. Cerutti and colleagues identify a RORγt-dependent innate lymphoid cell subset that establishes crosstalk among multiple cell types to enhance antibody responses.

How and when memory T cells emerge remains unresolved. Chang and colleagues use single-cell analyses to identify gene-expression signatures predictive of the eventual fates of individual CD8⁺ T cells during immune responses in vivo.

The transcription factor BATF is required for differentiation of certain helper T cell subsets. Haining and colleagues show that BATF crucially regulates CD8⁺ effector cells by coordinating a transcription factor network.

TCR ligation triggers the activation of multiple downstream signaling modules. Malissen and colleagues use quantitative proteomics to identify a Lat-independent TCR–CD6–SLP-76–Zap70 signalosome after TCR stimulation.

Hypoxia stabilizes the transcription factor HIF-1α, which promotes T_H17 polarization. Weiss and colleagues show that miR-210 mediates a negative feedback regulatory loop that diminishes HIF-1α abundance under hypoxic conditions.