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Sun and colleagues show that the deubiquitinase USP15 stabilizes expression of the E3 ubiquitin ligase MDM2 in T cells, which results in inhibition of T cell activation, and in cancer cells, which results in survival of cancer cells.
Natural killer (NK) cells help control viral infections and mediate antitumor responses. Joseph Sun and colleagues show the transcription factor Zbtb32 antagonizes Blimp-1 to mediate replicative bursts of NK cells.
Double-positive αβ thymocytes undergo negative selection on thymic epithelial cells. Ziegler and colleagues show that TGF-β limits numbers and function of medullary thymic epithelial cells, thus influencing the resultant T cell repertoire.
The transcription factor Foxp3 is essential for the function of regulatory T cells (Treg cells). Rudensky and colleagues show binding of Foxp3 poises target genes for repression and, after activation of Treg cells, recruits the histone methyltransferase Ezh2.
The kinase SGK1 is a downstream target of mTORC2 signaling. Powell and colleagues show that SGK1 regulates TH2 polarization by increasing the stability of the transcription factor JunB and antagonizing IFN-γ expression.
Signaling events at the Treg cell immune synapse remain unknown. Altman and colleagues show that a CTLA-4–PKC-η signaling axis is required for contact-dependent suppression by Treg cells.
Adaptors of the TRAF family are tumor-necrosis factor receptor–associated factors. So and colleagues show that TRAF5 negative regulates the IL-6 receptor signaling pathway, which limits the induction of proinflammatory CD4+ T cells.
The role of IL-6 in obesity-associated inflammation remains controversial. Bruening and colleagues identify signaling by IL-6 as an important determinant for the alternative activation of macrophages during inflammation.
Histone deacetylases (HDACs) are crucial regulators of cell identity. Ellmeier and colleagues show that HDAC1 and HDAC2 maintain CD4+ T cell lineage integrity by repressing Runx-CBFβ complexes in TH1 cells but not in TH2 cells.
The function of the lymphocyte-expressed receptor CD96 is almost entirely unknown. Smyth and colleagues demonstrate that it serves a key role in restraining activation of NK cells in part by competing with the activating receptor CD226 (DNAM-1).
The precise mechanisms of the thymic development Treg cells are still being determined. Farrar and colleagues demonstrate that signals from a triumvirate of members of the tumor-necrosis factor receptor superfamily are critical for Treg cell development in the thymus.
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.
Hypoxia stabilizes the transcription factor HIF-1α, which promotes TH17 polarization. Weiss and colleagues show that miR-210 mediates a negative feedback regulatory loop that diminishes HIF-1α abundance under hypoxic conditions.
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.
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.
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.
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.
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.
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.
Tyrosine phosphorylation of VE-cadherin affects endothelial junction integrity. Vestweber and colleagues show that two different tyrosine residues distinctly and selectively regulate vascular permeability or leukocyte extravasation.