DNA and RNA stimulate the mammalian innate immune system through activation of Toll-like receptors (TLRs). DNA containing methylated CpG motifs, however, is not stimulatory. Selected nucleosides in...

Communication between the central nervous system and the periphery contributes to stress responses and mood disorders. In a recent issue of Cell, Schneider et al. report that psychological stress...

Low doses of IL-2 can specifically activate regulatory T cells, making this an attractive therapeutic option for autoimmune diseases. Raeber et al. generated a comprehensive atlas of immune responses...

Recent studies revealed the existence of common principles of innate immune mechanisms across kingdoms and between the innate and adaptive branches of immunity in vertebrates. Lemaitre et al. discuss...

Lymph nodes (LNs) are critical for surveilling the tissue they drain. How LNs integrate and respond to complex cues in the situation of LN sharing between organs is unknown. Brown and Komnick et al....

Lipid nanoparticle-encapsulated, nucleoside-modified mRNA vaccines produce adaptive immune responses protective against COVID-19. Here, Pardi and colleagues review the innate immune-sensing pathways...

Wculek et al. uncover OXPHOS metabolism as a distinguishing feature among tissue macrophages in different organs in homeostasis. OXPHOS metabolism is required for maintenance of macrophage populati...

DAMPs represent important mediators in inflammation and inflammatory disease. Zhou et al. summarize the conversion route, classification, cellular origin, and sensing of DAMPs and their role in...

Neuroanatomical barriers are defended by the immune system to safeguard the CNS parenchyma from pathogens. Ampie and McGavern review the anatomy and development of CNS barriers as well as their...

Extracellular vesicles (EVs) are lipid bilayer nanovesicles that are released as ectosomes and exosomes with diversity in size and content. In this review, Kalluri examines the literature on the...

Regulatory T (Treg) cell accumulation in tumors suppresses antitumor immunity, but the mechanisms are incompletely understood. Here, Moreno Ayala et al. show that CXCR3 expression on Treg cells puts...

Glioblastoma is notorious for immunosuppression, but the mechanisms are unclear. Sattiraju et al. report that hypoxic zones in GBM attract and sequester tumor-associated myeloid cells and cytotoxic...

The activation of the innate immune system and subsequent neuroinflammation are common hallmarks of all neurodegenerative diseases. Castro-Gomez and Heneka review the emerging evidence related to...

The discovery of naive CD4+ T cell transcriptional heterogeneity raises the question regarding its plasticity and the mechanisms that may perturb the basal state. Even et al. report that, in mice,...

Mulder et al. integrate 178,651 human mononuclear phagocytes (MNPs) from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE) that enables the definition of conser...

Tissue-resident memory CD8+ T cells serve as a first-line defense against many pathogens. In this issue of Immunity, Buquicchio et al. unveil the epigenomic landscapes of virus-specific CD8+ T cell...

Fasting influences the distribution of leukocytes throughout the body, but its mechanisms and implications are only partly understood. Here, Janssen et al. reveal how fasting leads to homing of...

Females have greater immune responses to diverse antigens than males. Klein and colleagues review how signaling through receptors for estrogens, androgens, and progesterone directly regulate immune...

Manipulating exhausted T (Tex) cells has therapeutic implications. Pichler et al. found that the activating receptor, CD137 (4-1BB), was specifically expressed by Tex cells. CD137 signaling promoted...

The cGAS-STING pathway detects intracellular DNA and activates a potent antiviral response. Dvorkin and colleagues summarize recent insights into cGAS-STING biology and its role in host defense,...

In this perspective, Ginhoux, Yalin, Dutertre, and Amit outline the past, present, and future applications of single-cell genomics in immunology and discuss how the integration of multiomics at the...

Improved understanding of how the lung stroma contributes to the development of an immunosuppressive pre-metastatic niche could potentiate new anti-cancer treatments. Here, Gong et al. identify...

The BCG vaccine for tuberculosis protects against non-mycobacterial infections, but the mechanisms are unclear. Sun et al. found that BCG alters gene expression and chromatin accessibility in...

Epithelial cells (tuft and goblet cells) interact with immune cells on the “inside” while secreting effector molecules into the topological “outside.” In this issue of Immunity, Zhao et al. investi...

Memory T cells comprise circulating and tissue-resident subsets. In this issue of Immunity, Evrard et al. generate an imputed high-dimensional, single-cell protein expression atlas of memory CD8+...

Aging induces cellular senescence of immune cells, yet the underlying mechanism is poorly understood. Here, Zhou et al. reveal that type 2 cytokine signaling protects macrophages from senescence by...

Intestinal tuft cells are known as sentinels capable of initiating type 2 immune responses upon parasite infections. Ndjim et al. now report a direct effector function for intestinal tuft cells...

The transcription factor interferon regulatory factor 2 (IRF2) translates interferon signaling to regulate T cells. In this issue of Immunity, Lukhele et al. identify IRF2 in tumor-infiltrating...

Pittet and colleagues review the current knowledge of DC-T cell interactions at both priming and effector sites of immune responses and discuss how insights from DC development, ontogeny, and...

Immunotherapies against glioblastoma exhibit limited efficacy. Chen et al. examine the impact of immunotherapy in mesenchymal glioblastomas and find that αCTLA-4 treatment promotes tumor suppression...

Despite barriers that isolate the intestinal lumen and compartmentalize the nervous system, some microbial molecules can penetrate these barriers to act directly on brain tissues. In this review,...

Low doses of IL-2 can specifically activate regulatory T cells, making this an attractive therapeutic option for autoimmune diseases. Raeber et al. generated a comprehensive atlas of immune responses...

Alternatively activated macrophages (AAMs) promote the resolution of inflammation and tissue repair. Faas et al. show that the alarmin IL-33 promotes a mitochondrial rewiring of macrophages and the...

Recent advances in the field of sepsis have revealed that subgroups of patients can be identified with distinct phenotypic and pathobiological features. van der Poll and colleagues review these new...

Giles et al. generated an epigenomic T cell differentiation atlas from healthy human donor (HD) blood. This atlas was used to (1) identify transcriptional and epigenetic modules in human CD8 T cell...

Franken et al. examine the mechanisms that differentiate combined therapy with anti-CTLA4 and anti-PD-L1 from anti-PD-L1 monotherapy in head and neck squamous cell carcinoma (HNSCC). Single-cell...

Macrophages of distinct origin and function populate tumors. Nixon et al. examine how cancer impacts mononuclear phagocytic antigen-presenting cells and find that monocyte-derived tumor-associated...

The role that B cell receptor (BCR) signaling plays in selection within germinal centers (GCs) is not well understood. Here, Chen et al. demonstrate that BCR signaling is necessary for the survival...

SARS-CoV-2 mRNA-based vaccine-induced immunity is thought to wane quickly based on short-term studies. Using longitudinal data, Srivastava et al. find that participants with hybrid immunity show...