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The cytidine deaminase AID is essential for the immunoglobulin-diversification processes. Chaudhuri and colleagues identify the splicing factor PTBP2, which promotes the binding of AID to switch-region DNA.
Ldb1 functions as a core component of various multiprotein transcription complexes. Love and co-workers show a continuous requirement for Ldb1 in the maintenance of both fetal and adult HSC.
Pathways dependent on the transcription factor NF-κB provide innate immunity against microbes. Karin and colleagues show that mice lacking the kinase IKKβ have IL-1-dependent neutrophilia. Loss of IL-1 signaling restores blood cellularity but severely compromises antimicrobial defense.
Transcription factors specific for helper T cell lineages, such as T-bet, counter-regulate helper T cell development, but the details of this remain unclear. Glimcher and colleagues unravel the molecular basis of the regulation of TH17 cells by T-bet.
Immunoglobulin genes are further diversified by the cytidine deaminase AID. Gearhart and colleagues show immunoglobulin genes accumulate AID-dependent uracil residues within the first 24 hours of B cell stimulation.
Peptides presented to cytotoxic T lymphocytes are typically generated by proteasome action. Kessler and colleagues show that the cytosolic endopeptidases nardilysin and thimet oligopeptidase generate the C termini of tumor-relevant epitopes.
Autophagy is a physiological process that involves the engulfment and degradation of organelles. Choi and colleagues demonstrate that autophagy is important for the removal of damaged mitochondria and thus the control of inflammation.
TGF-β and Foxp3 are required for the development of regulatory T cells. Chen and colleagues show that the helix-loop-helix proteins E2A and Id3 enhance Foxp3 expression and relieve it from inhibition by other transcription factors.
HLA-DM activity ensures that only high-affinity peptides are displayed on MHC class II molecules. Wucherpfennig and colleagues show that interaction of HLA-DR with the N terminus of bound peptides determines susceptibility to HLA-DM.
The molecular basis of TH2 lineage commitment is poorly understood. Kubo and colleagues identify the Il4 enhancer HS2 as a target of the transcription factor GATA-3 and show it to be critical for IL-4 production and TH2 functional commitment.
Binding of the transcription factor NF-κB subunit RelA activates proinflammatory gene expression. Gozani and colleagues show that basal expression of RelA target genes is suppressed by methylation of RelA by SETD6, which triggers repressive histone methylation by GLP.
Immunoglobulin genes are prominent targets of the deaminase AID. Casellas and Nussenzweig and co-workers show that whereas stalled polymerases recruit AID across the B cell genome, efficient hypermutation is restricted to immunoglobulin loci by the RPA cofactor of AID.
Poly(ADP-ribose) polymerases participate in many biological and pathological processes. Takaoka and co-workers show that the short isoform of PARP-13 (ZAPS) is selectively induced by 5'-triphosphate–modified RNA and regulates signaling mediated by the RNA helicase RIG-I.
Pyroptosis is a form of proinflammatory cell suicide whose physiological importance is unclear. Aderem and colleagues show that pyroptosis can be integral to protection against bacterial infection.
The heterodimeric cytokine IL-27 consists of the subunits p28 and EBI3. Hunter and colleagues demonstrate that p28 acting alone can inhibit the signaling of many cytokines by interfering with the common receptor gp130.
Plasma cells are antibody-producing factories. McHeyzer-Williams and colleagues report that they can also act in a negative feedback loop to dampen the recruitment and activity of antigen-specific follicular helper T cells.
The functions of the human T cell repertoires that recognize different CD1 molecules remain unknown. Moody and co-workers show that many CD1a-autoreactive T cells home to skin, where they produce IL-22.
The kinase Zap70 transmits downstream signals after TCR ligation. Weiss and colleagues describe a conditional Zap70 catalytic mutant that demonstrates kinase-independent functions in regulatory T cells.
NK cells confer innate immune functions. Von Andrian and colleagues show that hepatic NK cells bearing CXCR6 receptors confer antigen-specific NK cell memory that is protective against various viruses.
IL-35 is an immunomodulatory cytokine secreted by regulatory T cells. Vignali and colleagues demonstrate that IL-35 also mediates the induction of a unique regulatory population that may underpin infectious tolerance.