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Regulatory T (Treg) cells are needed to suppress autoreactive immune cell responses. Murre and colleagues show the transcriptional regulators Id2 and Id3 are necessary for proper Treg cell development, homing and maintenance.
The kinase mTOR is important in lymphocyte bioenergetics but has not been examined in natural killer cells. Walzer and colleagues demonstrate that mTOR is key to sustaining the proliferation and effector function of these cells.
TH9 cells are associated with autoinflammatory diseases. Apetoh and colleagues demonstrate a molecular pathway which converts TH9 cells into potent anticancer cells.
Various endogenous and pathogen-derived stimuli trigger the assembly of cytosolic multimolecular 'speck' platforms coordinated by the adapter ASC. Latz and colleagues demonstrate that ASC specks have extracellular functions that can prolong inflammation.
Type III interferons have important antiviral functions, but they are poorly described compared to type I interferons. Kagan and colleagues demonstrate that type III interferons are induced on peroxisomes in response to a variety of viral triggers.
The NLRP3 inflammasome is involved in IL-1 production and pyroptosis. Pelegrín et al. demonstrate that it is also released extracellularly as a functional proinflammatory particle.
The TH9 subset of helper T cells has specialized roles in parasite immunity. Neurath and colleagues show that TH9 cells are also important for the pathogenesis of mouse and human colitis by disrupting gut barrier function.
TCR ligation activates the kinase Zap70. Weiss and colleagues, utilizing 'analog-sensitive' Zap70 cells, show that thymocyte positive and negative selection exhibit differential temporal requirements for Zap70 signaling.
Prior antigenic exposure induces cognate memory responses in B cells. Shlomchik and colleagues show that CD80 and PD-L2 define functionally distinct memory B cells.
Lineage fate in the thymus is imposed by the antagonizing effects of the transcription factors ThPOK and Runx3. Park and colleagues show that ThPOK-induced SOCS factors are required for differentiation into the CD4+ T cell lineage.
The molecular mechanisms that regulate the induction of follicular helper T cells (TFH cells) remain unclear. Liu and colleagues show that the E3 ubiquitin ligase Itch regulates TFH cell differentiation through ubiquitination and degradation of the transcription factor Foxo1.
The cell-intrinsic factors that regulate the differentiation of follicular helper T cells remain unclear. Hu and colleagues demonstrate that the transcription factor Foxp1 is critical in inhibiting such differentiation.
NF-κB activity is regulated by multiple ubiquitin-dependent regulatory steps. Cao and colleagues show that the rhomboid protein Rhbdd3 recognizes K27-linked ubiquitin and prevents IL-6-mediated autoimmunity by recruiting the deubiquitinase A20 to NEMO (IKKγ) kinase complexes.
TCF-1 and LEF-1 are essential for early T cell development. Xue and colleagues show that in DP thymocytes, they control CD4+-versus-CD8+ T cell lineage 'decisions' and contribute to the establishment of CD8+ T cell identity.
Antigen-bearing dendritic cells transit through the lymphatics via chemokine receptor CCR7–dependent chemotactic cues. Rot and colleagues show that the atypical chemokine receptor CCRL1 establishes chemokine polarity in the subscapsular sinus that enables entry into the lymph node.
Regulatory T cells proliferate robustly in gut lymphoid tissues. Hase et al. show that this proliferation requires their expression of the epigenetic regulator Uhrf1, which is increased in response to IL-2 produced by effector T cells.
Double-stranded DNA (dsDNA) in the cytoplasm triggers IL-1β production as an antiviral response. Ruland and colleagues describe the formation of dsDNA-Rad50-CARD9 signaling complexes for NF-κB activation and the generation of pro-IL-1β after infection with a DNA virus.
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.