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Monoclonal antibody (mAb) therapy is now commonplace in the clinic, yet such reagents can elicit unwanted side effects due to interactions with Fcγ receptors. Georgiou and colleagues have engineered mAbs that lack such FcγR interactions but retain the ability to activate complement and show that these modified mAbs have efficacious effector function.
Various intracellular pathogens attempt to hide from innate cytosolic sensors by forming vacuoles. Yamamoto and colleagues show that the autophagy-related protein Gate-16, which is induced by interferon-γ, is required for noncanonical autophagy to control infection by Toxoplasma gondii.
Xue and colleagues show that Runx3−/− CD8+ T effector cells aberrantly upregulate genes characteristic of TFH cell lineage and exhibit impaired induction of cytotoxic molecules.
Thymocytes must undergo positive selection to survive and emigrate to the periphery as mature T cells. Glimcher and colleagues identify CHMP5 as a TCR-sensitive regulator of positive selection that acts by preventing oxidation and degradation of the pro-survival protein Bcl-2.
Single-nucleotide polymorphisms in the gene encoding the cytosolic viral sensor IFIH1 are linked to a variety of autoimmune diseases. Rawlings and colleagues demonstrate that one such common polymorphism results in IFIH1 with more-potent activation and can act synergistically with other genetic backgrounds to manifest autoimmune disease.
Genetic polymorphisms affect expression of the atypical chemokine receptor ACKR1 (Duffy) on nucleated erythrocyte precursors. Rot and colleagues show that loss of its expression alters hematopoiesis, yielding a distinct neutrophil population that rapidly exits the bloodstream to give an apparent ‘neutropenia’ phenotype.
TCRβ+CD8αα+ intraepithelial lymphocytes arise from CD4−CD8−CD5+ thymic cells, but the exact precursor source has been not been established. Hogquist and colleagues identify two distinct thymic populations that both give rise mainly to gut-homing intraepithelial lymphocytes.
BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.
Wucherpfennig and colleagues show that the microRNA miR-31 increases the sensitivity of T cells to type I interferons, which interferes with effector T cell function during chronic infection.
Jackson and colleagues show that dendritic cells transit to the lumen of lymphatic vessels through hyaluronan-mediated interactions with the endothelial receptor LYVE-1.
Hippo signaling controls cell and tissue growth. Geng et al. show that Hippo signaling is required for TH17 cell differentiation but inhibits Treg cell differentiation.
Intracellular detection of viral invasion triggers activation of the transcription factor IRF3 and antiviral interferon production. Fangfang Zhou and colleagues report that the transcription regulator YAP in the host restrains this process by preventing inadvertent spontaneous dimerization of IRF3 and its translocation to the nucleus.
Microglia are the tissue-resident macrophages of the brain. Ouyang and colleagues show the ER-resident transmembrane protein NRROS is necessary for proper development and function of microglia. Mice lacking NRROS exhibit neurologic defects and die prematurely.
Neonates are thought to have impaired immune responses, yet, paradoxically, they can also demonstrate hyperinflammation. Ulas et al. show that a neonatal burst of the alarmins S100A8 and S100A9 activates a distinct innate immune response without dangerous hyperinflammation.
Macrophages serve important functions in defense and tissue homeostasis. Jung and colleagues demonstrate that a resident population of macrophages controls the innervation of brown adipose tissue and thereby regulates energy use.
IgA is necessary for maintaining gut homeostasis, and its production depends on microbial sampling by the gut-associated lymphoid tissue (GALT). Takayanagi and colleagues identify a novel population of mesenchymal cells in the GALT that control M cell differentiation and function of gut epithelium.
Loke and colleagues show that vitamin A is required for the conversion of interleukin 4 (IL-4)-activated monocyte-derived macrophages into macrophages with a tissue-resident phenotype in the peritoneal cavity and in S. mansoni–induced liver granulomas in mice.
Obesity is commonly accompanied by inflammatory responses in white adipose tissues. Chavakis and colleagues identify a vicious cycle involving α4 integrins and the adhesion molecule VCAM-1 that promotes inflammatory macrophage–adipocyte interactions and suppresses beige adipogenesis.
Turner and colleagues show that the RNA-binding protein ZFP36L1 regulates a post-transcriptional hub that determines the identity of marginal-zone B cells by promoting their localization and survival.
Transcription factors compete for superenhancer sites and have antagonist functions. Farrar and colleagues identify regulatory competition between STAT5 and IKAROS or NF-κB in B cells and show that the ratio of STAT5 to IKAROS or to NF-κB can serve as a prognostic marker of disease severity of the leukemia B-ALL.