Issues
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Cover Image
Cover Image
ON THE COVER
Reed-Geaghan et al. use genetic labeling to demonstrate that resident microglia are the only myeloid cell present at β-amyloid plaques.The cover image shows co-localization of activated microglia marker Iba1 (green) with a marker for resident microglial cells (tdTomato in red) in an 8-mo-old AD model mouse. Image provided by authors. Image © Reed-Geaghan et al., 2020. https://doi.org/10.1084/jem.20191374 - PDF Icon PDF LinkTable of Contents
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Viewpoint
Drugging the microbiome
Cathryn R. Nagler discusses the opportunities of creating new microbiome-based drugs.
Insights
The omentum, a niche for premetastatic ovarian cancer
Omentum-resident macrophages of embryonic origin facilitate ovarian cancer metastasis
Microglia in Alzheimer’s disease: Local heroes!
Resident microglia are the primary source of myeloid cells present at β-amyloid deposits.
Reviews
A critical role for plasminogen in inflammation
Plasminogen, primarily a blood protein involved in fibrinolysis, also participates in inflammatory processes throughout the body. Baker and Strickland summarize the role of plasminogen and its activator system in regulating inflammation in health and disease.
Unfolding innate mechanisms in the cancer microenvironment: The emerging role of the mesenchyme
Koliaraki et al. provide a concise overview of the role of the innate system in cancer, including the recruitment, activation, and functions of innate immune cells and the emerging tumor modulatory innate properties of fibroblastic mesenchyme.
The blood–brain barrier in health and disease: Important unanswered questions
The blood vessels of the central nervous system tightly control the movement of ions, molecules, and cells between the blood and tissue. This “blood–brain barrier” is vital for neural homeostasis and protection. This review discusses current knowledge of the blood–brain barrier, emphasizing key unanswered questions.
Brief Definitive Reports
Transcriptional profiling identifies caspase-1 as a T cell–intrinsic regulator of Th17 differentiation
Gao et al. reveal that DCs shape a distinct pathogen-specific CD4 T cell transcriptome and discover an unexpected role for T cell–intrinsic caspase-1 in promoting Th17 differentiation.
Plaque-associated myeloid cells derive from resident microglia in an Alzheimer’s disease model
Fate mapping of resident microglia and peripheral monocytes reveals that the myeloid cells that migrate to and associate with amyloid plaques in a mouse model of Alzheimer’s disease are exclusively derived from resident microglia.
Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development
Choi et al. identify mice with a metabolic disorder and severe lymphoid and myeloid hypoplasia resulting from mutation of PDIA6. The ER-resident oxidoreductase PDIA6 is necessary for folding of stroma-derived Wnt3a, BAFF, and IL-7 proteins, which are necessary for hematopoiesis.
Tumor-derived soluble CD155 inhibits DNAM-1–mediated antitumor activity of natural killer cells
This report demonstrated that soluble CD155 interferes with the DNAM-1–mediated antitumor immunity mediated by NK cells and promotes lung colonization of B16/BL6 melanoma cells.
Cell-intrinsic adrenergic signaling controls the adaptive NK cell response to viral infection
Natural killer (NK) cells are critical for protection against viruses. Diaz-Salazar et al. show that adrenergic neurons modulate the adaptive NK cell response in a cell-intrinsic manner. This study identifies the nervous system as a novel axis through which antigen-specific NK cell responses are regulated.
β2-adrenergic signals downregulate the innate immune response and reduce host resistance to viral infection
Stress hormones increase host susceptibility to viral infection. β2-adrenergic signals in nonhematopoietic cells downmodulate the proinflammatory antiviral natural killer cell response, which is necessary for efficient pathogen elimination. This modulation increases the severity of tissue lesions, decreasing resistance to infection.
Tissue-specific pathways extrude activated ILC2s to disseminate type 2 immunity
Activated ILC2s can enter circulation after migratory helminth infection. Using fate-mapping, alarmin-specific knockouts, and methods to isolate tissue-specific perturbations, the authors demonstrate that ILC2 extrusion from tissues reflects activation of pathways specific to receptors on the resident ILC2 population.
Articles
Activation of group 2 innate lymphoid cells alleviates aging-associated cognitive decline
Fung et al. show that group 2 innate lymphoid cells (ILC2) accumulate in the choroid plexus (CP) of the aged brain. These aging-associated CP-resident ILC2 exhibit unique functional and molecular properties, and their activation revitalizes the aged brain and alleviates aging-associated cognitive decline.
Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension
This study shows that the cAMP/Epac1 pathway plays a critical role in retinal neurodegeneration via CaMKII activation in mouse models of ocular hypertension and suggests that Epac1 is a therapeutic target for neuroprotection in glaucoma.
Tissue-resident macrophages in omentum promote metastatic spread of ovarian cancer
Etzerodt et al. identify a unique subset of CD163+ Tim4+ tissue-resident macrophages in omentum that are maintained independently of bone marrow–derived monocytes and have a specific role in the metastatic spread of ovarian cancer cells.
Mutation position is an important determinant for predicting cancer neoantigens
Cancer mutations create neoantigens that are of great interest for immunotherapy, but their accurate identification remains a challenge. Capietto et al. show that mutation position is an important determinant for immunogenicity, and incorporating this feature into prediction algorithms improves their identification.
The colonic macrophage transcription factor RBP-J orchestrates intestinal immunity against bacterial pathogens
Transcription factor RBP-J in intestinal macrophages dynamically controls antibacterial immunity by interfacing with T cells and ILCs. Macrophage-intrinsic RBP-J supports intestinal Th17 cell responses via IL-6 production, whereas RBP-J deficiency unexpectedly reveals a compensatory role for ILC3 late during infection.
Macrophage galactose lectin is critical for Kupffer cells to clear aged platelets
Deppermann et al. investigate how aged platelets are removed from circulation. Using intravital microscopy they observe rapid accumulation of desialylated platelets on Kupffer cells through collaboration of macrophage galactose lectin and Ashwell-Morell receptor. Effective clearance is critical, as mice with an aged platelet population bleed.
Sequential ubiquitination of NLRP3 by RNF125 and Cbl-b limits inflammasome activation and endotoxemia
Hyper-activation of NLRP3 inflammasomes contributes to the development of endotoxemia, but the molecular mechanisms are poorly defined. Tang et al. demonstrate that sequential ubiquitination of NLRP3 is crucial to keep NLRP3 inflammasomes in check and limits endotoxemia.
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