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The molecular mechanisms behind recognition of altered self remain unclear. Moore and co-workers show that oxidized low-density lipoprotein (LDL) and β-amyloid trigger inflammatory signaling through a heterodimer of Toll-like receptors 4 and 6.
CTLA-4-deficient mice develop a lethal multiorgan lymphoproliferative disorder. Murphy and colleagues definitively demonstrate that at least some of the pathogenic T cells that drive this disorder show reactivity to nonlymphoid tissue self antigens.
The signaling intermediates that activate inflammasomes have remained elusive. Tschopp and co-workers now describe that a thioredoxin-binding protein is a reactive oxygen species–regulated component of the NLRP3 inflammasome.
Natural killer cells infiltrate the pancreas during type 1 diabetes. Mandelboim and co-workers find that the natural killer receptor NKp46 recognizes ligands on pancreatic beta cells and is essential for full diabetes development.
Pre-TCR signaling is essential for the passage of thymocytes through the β-selection checkpoint. Ravichandran and co-workers find that CXCR4 acts as a costimulator for the pre-TCR and is needed for optimal progression through β-selection.
TCR movement in the T cell plasma membrane is not well understood. Using three different types of microscopy, Davis and co-workers identify separate islands of Lat and TCR molecules that concatenate after T cell activation.
Immunoglobulin diversification is absolutely dependent on the action of activation-induced cytidine deaminase, which must be tightly controlled. Honjo and colleagues systematically analyze the regulatory elements that govern expression of the gene encoding this deaminase.
Toll-like receptor (TLR) signaling activates the transcription factor NF-κB and production of proinflammatory cytokines. O'Neill and colleagues show that TLR signaling induces the microRNA miR-21 to dampen PDCD4 expression, which leads to less NF-κB activity and more IL-10 production.
B cell development requires interleukin 7 signals that activate the transcription factor STAT5. Busslinger and colleagues report that STAT5 has a permissive rather than instructive role in pro-B cell survival and immunoglobulin recombination.
Naive CD4+ T cells can differentiate into distinct polarized effector cells, but detailed characterization of physiologic CD4 memory is lacking. Jenkins and colleagues show that TH1 and TH17 memory cells differ in longevity and arise via different infection routes.
Production of mature interleukin 1β (IL-1β) requires Il1b transcription and inflammasome-mediated processing of IL-1β protein. Ruland and colleagues show that the RNA virus sensor RIG-I signals via the adaptors CARD9 and Asc to facilitate both processes.
TLR4 signals via MyD88 and TRIF to activate proinflammatory cytokine and type I interferon responses. Karin and colleagues show that different ubiquitination of TRAF3 via K48 or K63 dictates the ensuing immune response.
Autophagy facilitates host defense against invading bacteria. Philpott and colleagues show that Nod1 and Nod2 link pathogen sensing to autophagy by recruiting the autophagy protein AGT16L1 to the site of pathogen entry.
High-affinity and isotype-switched antibodies arise from germinal center reactions. Goodnow and colleagues identify the Rho guanine nucleotide–exchange factor DOCK8 as being essential for sustained B cell immune synapse formation in germinal centers and mature antibody responses.
The mitochondrial adaptor MAVS is necessary for the transmission of RIG-I and Mda5 antiviral signals. Jiang and colleagues show that PCBP2 negatively regulates MAVS stability by recruiting the L48-ubiquitinating enzyme AIP4, thereby preventing excessive cytokine responses.
The molecular mediators responsible for directing T helper type 2 (TH2) differentiation remain incompletely defined. Dong and co-workers find that the transcription factor Dec2 promotes expression of the transcription factor JunB and is essential for the induction of TH2 responses.
Nod2 senses intracellular bacteria and is required for their eradication. Nuñez and co-workers now describe a T cell–intrinsic role for Nod2 in combating the intracellular parasite Toxoplasma gondii.
Immunization elicits B cell memory and short- and long-term antibody-secreting plasma cells. Weill and colleagues show that long-term IgM+ and IgG+ memory B cells can persist in germinal centers and undergo different fates after antigenic rechallenge.
Defensins combat pathogenic bacteria invading the mammalian intestine. Salzman and co-workers find that defensins influence the composition of the small intestinal commensal microbiota and the presence of interleukin 17–producing T cells in the lamina propria.
Interleukin 17 (IL-17)-producing helper T cells (TH-17 cells) are associated with the pathogenesis of multiple sclerosis. Pei and colleagues have now identified a TH-17 cell–associated microRNA, miR-326, whose expression correlates with disease severity in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis.