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The deubiquitinase A20 is a negative regulator of transcription factor NF-κB signaling pathways. Ma and colleagues show that mice lacking A20 expression in dendritic cells have defective lymphocyte homeostasis and develop spontaneous inflammatory disease.
The TH17 subset of helper T cells can produce interleukins IL-17 and IL-22, although regulation of these cytokines expression differ. Ouyang and colleagues show that TGF-β induces upregulation of the transcription factor c-Maf, which suppresses IL-22 expression.
IL-17C is induced in epithelia by bacterial and inflammation stimuli. Pappu and colleagues show that IL-17C signals in an autocrine manner through the IL-17RA-IL-17RE receptor complex to regulate epithelial immune responses.
IL-17RE is an orphan receptor of the IL-17 receptor family. Qian and colleagues identify IL-17RE as the receptor specific for IL-17C signaling in mucosal defense against intestinal pathogens.
The adaptor LRRK2 has been identified as a major susceptibility factor for Crohn's disease. Lenardo and colleagues show that LRRK2 negatively regulates activation of the transcription factor NFAT independently of NFAT phosphorylation.
The enzyme that directly activates the kinase PKC-θ during T cell antigen receptor signaling is still unknown. Tan and colleagues show that the serine-threonine kinase GLK is a direct activator of PKC-θ.
The cellular sources of IL-9 in lung inflammation remain unknown. Stockinger and colleagues use an IL-9 reporter to show IL-9 production is restricted to innate lymphoid cells during papain-induced lung inflammation.
Production of MHC class I epitopes involves the proteasome and multiple peptidases. Bernstein and colleagues show that angiotensin-converting enzyme (ACE) contributes to the generation of this peptide repertoire by trimming carboxyl termini.
Establishing effector memory cells at mucosal barriers is critical for immune protection against pathogens. Cheroutre and colleagues show that interactions between thymus leukemia antigen and CD8αα contribute to the generation of CD8αβ+ effector memory T cells.
Antigen recognition by surface immunoglobulin triggers downstream signaling and endocytosis of B cell antigen receptors. Pierce and colleagues show that distinct kinase-activation patterns distinguish surface receptor signaling from that of internalized receptors.
The kinase PKC-θ translocates to the center of the immune synapse, but the molecular basis of this interaction is unclear. Altman and colleagues identify a conserved proline-rich motif in the V3 domain of PKC-θ required for its association with CD28 and localization to the immunological synapse.
Cytokine-producing innate lymphoid cells are found at mucosal surfaces. Artis and Wherry and their colleagues show that innate 'nuocyte-like' cells accumulate in virus-infected lungs and contribute to the repair of tissues.
Efficient T cell priming occurs in organized lymphoid tissues. Turley and colleagues show that activated T cells induce nitric oxide production by lymph node stromal cells, thus limiting T cell proliferation.
The development of RORγt+ innate lymphoid cells (ILCs) remains poorly defined. Golub and colleagues define the stages of fetal and adult RORγt+ ILC maturation and show that adult RORγt+ ILCs mature outside the bone marrow, in a Notch2-dependent manner.
Mice have lineage-negative IL-7Rα+ (innate lymphoid) cells that contribute to type 2 immunity. Spits and colleagues identify a similar CRTH2+CD161+ population in human lungs and gut that produces IL-13 after stimulation.
Natural killer T cells recognize glycolipid ligands in the context of the antigen-presenting molecule CD1d. Kronenberg and colleagues show that these cells recognize ligands derived from the pathogens Streptococcus pneumonia and group B Streptococcus.
Sensors of cytosolic nucleic acid can detect the presence of viruses. Liu and colleagues identify the helicase DDX41 as a sensor of double-stranded DNA that initiates upregulation of type I interferon dependent on the adaptor STING in myeloid DCs.
The adaptor ASC functions in inflammasome assembly. Kanneganti and colleagues show that ASC has an inflammasome-independent role in regulating the stability of Dock2 mRNA and thereby governs the chemotaxis and phagocytosis of cells of the immune response.
Viral microRNAs can modulate a variety of host genes. Ahn and colleagues identify a human cytomegalovirus microRNA that downregulates the peptide-processing enzyme ERAP1 and prevents presentation of antigenic viral peptides.
The cytidine deaminase APOBEC3G has an important intrinsic antiviral function. Collins and colleagues show that APOBEC3G can also trigger a protective natural killer cell response by damaging host DNA.