Issues

Cathryn R. Nagler discusses the opportunities of creating new microbiome-based drugs.

Omentum-resident macrophages of embryonic origin facilitate ovarian cancer metastasis

Resident microglia  are the primary source of myeloid cells present at β-amyloid deposits.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.