Generalized pustular psoriasis (GPP) is a rare human autoinflammatory disorder with life-threatening systemic effects. Keratinocyte-derived interleukin (IL)-36 signaling has been identified as a key mediator of immune response in the skin of affected individuals. Recognition of various mutations along the IL-36 axis and the downstream nuclear transcription factor κB (NF-κB) signaling have established GPP as genetically, immunologically, and histopathologically distinct and amenable to immunomodulation, which is epitomized by the recent success of IL-36 antagonism. This review covers recent discoveries of the genetic and immunological underpinnings of GPP, which have proved fertile ground for improving the quality of care of this clinically challenging and debilitating condition.

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but are frequently associated with immune-related adverse events (irAEs). This article offers a novel synthesis of findings from both preclinical and clinical studies, focusing on the molecular mechanisms driving irAEs across diverse organ systems. It examines key immune cells, such as T cell subsets and myeloid cells, which are instrumental in irAE pathogenesis, alongside an in-depth analysis of cytokine signaling [interleukin (IL)-6, IL-17, IL-4), interferon γ (IFN-γ), IL-1β, tumor necrosis factor α (TNF-α)], integrin-mediated interactions [integrin subunits αITGA)4 and ITGB7], and microbiome-related factors that contribute to irAE pathology. This exploration of modifiable pathways uncovers new opportunities to mitigate irAEs by using available antibodies (Abs) that target key inflammatory molecules across tumor types, while ideally preserving the antitumor efficacy of ICIs.

Diverse macrophage populations inhabit the rodent and human central nervous system (CNS), including microglia in the parenchyma and border-associated macrophages (BAMs) in the meninges, choroid plexus, and perivascular spaces. These innate immune phagocytes are essential in brain development and maintaining homeostasis, but they also play diverse roles in neurological diseases. In this review, we highlight the emerging roles of CNS macrophages in regulating vascular function in health and disease. We discuss that, in addition to microglia, BAMs, including perivascular macrophages, play roles in supporting vascular integrity and maintaining blood flow. We highlight recent advancements in understanding how these macrophages are implicated in protecting against vascular dysfunction and modulating the progression of cerebrovascular diseases, as seen in vessel-associated neurodegeneration

Tumor-initiating cells (TICs) are particularly efficient at evading detection and elimination by the human immune system. Recent data from Yang and collaborators demonstrate that – at least in preclinical hepatocellular carcinoma models – the immunological privilege of CD49f+ TICs can be limited by targeting CD155, resulting in restored sensitivity to immune checkpoint inhibitors.

When B cells engage in an immune response, metabolic reprogramming is key to meeting cellular energetic and biosynthetic demands. Epstein–Barr virus (EBV) is a highly prevalent gamma-herpesvirus, latently infecting B cells for the human host’s lifetime. By hijacking signaling pathways of T cell-dependent humoral immunity, EBV activates B cells in a T cell-independent manner, forcing lymphoblastoid transformation. Interlinked with this coercion of signaling pathways, EBV has also evolved strategies to manipulate B cell metabolism. In this opinion article we integrate recent findings from studies of B cell metabolic reprogramming after EBV infection and during antigen-specific activation, respectively. We hypothesize that defining EBV host-cell metabolic vulnerabilities that differ from pathways required for B cell immunity might uncover novel therapeutic targets against EBV-related diseases.

Laboratory mice housed under specific pathogen–free (SPF) conditions are the standard model in biomedical research. However, experiments with a particular inbred mouse strain performed in different laboratories often yield inconsistent or conflicting data due to housing-specific variations in the composition and diversity of SPF microbiota. These variations affect immune and nonimmune cell functions, leading to systemic physiological changes. Consequently, microbiota-dependent inconsistencies have raised general doubts regarding the suitability of mice as model organisms. Since stability positively correlates with biological diversity, we postulate that increasing species diversity can improve microbiota stability and mouse physiology, enhancing robustness, reproducibility, and experimental validity. Similar to the generation of inbred mouse strains in the last century, we suggest a worldwide initiative to define a transplantable ‘wild’ microbiota that stably colonizes mice irrespectiv

Biomolecular condensates are membraneless organelles formed through liquid–liquid phase separation. Innate immunity is essential to host defense against infections, but pathogens also harbor sophisticated mechanisms to evade host defense. The formation of biomolecular condensates emerges as a key biophysical mechanism in host–pathogen interactions, playing pivotal roles in regulating immune responses and pathogen life cycles within the host. In this review we summarize recent advances in our understanding of how biomolecular condensates remodel membrane-bound organelles, influence infection-induced cell death, and are hijacked by pathogens for survival, as well as how they modulate mammalian innate immunity. We discuss the implications of dysregulated formation of biomolecular condensates during host–pathogen interactions and infectious diseases and propose future directions for developing potential treatments against such infections.

Gopee and colleagues’ recent analyses of diverse high-dimensional datasets of prenatal and adult skin, together with data from complex skin organoids, uncover the important contributions of macrophages in modulating prenatal skin development, scarless wound healing, and angiogenesis. These findings identify a role for skin immune cells in tissue development.

Chronic antigen exposure is frequently associated with T cell exhaustion. In a recent study, Aljobaily et al. show that pancreatic islet-infiltrating CD4+ T cells in mouse autoimmune diabetes may circumvent exhaustion by preserving TCF1 expression. Continuous recruitment of epigenetically pre-programmed CD62L+ CD4+ T cells seems to sustain the local autoimmune response.