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Positive selection of thymocytes is controlled by TCR expression and signaling. Lu and colleagues describe a previously uncharacterized protein, Tespa1, which associates with TCR signaling components and has a critical role in positive selection.
The eukaryotic translation-initiation factor eIF4E is a rate-limiting factor in protein translation. Sonenberg and colleagues show that phosphorylation of eIF4E modulates the antiviral response by selectively stimulating translation of the NF-κB inhibitor IκBα
TRIM28 is a nuclear protein associated with repressive heterochromatin. Honjo and colleagues show that loss of TRIM28 in T cells alters peripheral T cell homeostasis and regulatory T cell function, which leads to autoimmunity.
Polarized CD4+ T cells can demonstrate considerable plasticity depending on the cytokine milieu they encounter. O'Shea and colleagues show that retinoic acid induces the microRNA miR-10a, which suppresses the transcription factor Bcl-6 to prevent conversion into follicular helper T cells.
The role of costimulation in negative selection is controversial. Singer and colleagues demonstrate that it is critical for clonal deletion and its absence results in the diversion of thymocytes to an intraepithelial lymphocyte population.
Major histocompatibility complex (MHC) molecules are known to mediate reverse signaling. Cao and colleagues show that reverse signaling via MHC class I attenuates Toll-like receptor–triggered innate inflammatory responses through an Fps–SHP-2 pathway.
The aminopeptidase ERAAP trims peptides loaded onto MHC class I molecules and can be targeted during evasion of the immune response by pathogens. Shastri and colleagues show that inhibition of ERAAP identifies a protective nonclassical MHC presentation pathway involving Qa-1.
The processes that underlie maintenance of the identity of regulatory T cells are unclear. Sun and colleagues show that expression of the ubiquitin-conjugating enzyme Ubc13 by these cells is critical for this process.
Discriminating between pathogens and commensals is a major dilemma faced by the immune system. Nunez et al. demonstrate that the recognition of bacterial pathogen type III secretion systems by the NLRC4 inflammasome is key to this discrimination.
Follicular helper T cells provide help to cognate B cells in germinal centers to boost humoral immunity. Nutt and colleagues generate IL-21–GFP reporter mice to track the fate of follicular helper T cells.
Periodontitis is associated with aging and more neutrophil-mediated tissue pathology. Hajishengallis and colleagues show an inverse correlation between interleukin 17 expression and Del-1 expression in gingival tissues, with Del-1 protecting tissues from neutrophil infiltration.
Neutrophils are early responders and must navigate using spatial cues to arrive at infection sites. Xu and colleagues show that the opposing activities of MAP kinases Erk and p38 govern neutrophil migration.
The identity of the self lipids presented by CD1d that select iNKT cells is controversial. De Libero and colleagues identify ether-bonded self lipids generated by the peroxisome enzyme GNPAT can select developing iNKT cells in the thymus.
TH1 and TFH 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.
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.
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.
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.
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.
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.