Issues

ILC2 are critical regulators of inflammation and tissue homeostasis in diverse anatomical sites. ILC2-targeted mouse models have underpinned this emerging field of research. Kabil et al. (2025) developed a novel Il17rbCreERT2.eGFP mouse to study the role of Rora in mature ILC2.

Influenza virus remains a public health burden for which recommendations encourage annual vaccination. However, some studies have suggested repeat annual vaccination may have negative effects on influenza virus immunity. This review analyzes immunological mechanisms that may result in reduced effectiveness of annual influenza virus vaccines.

We highlight how the gut microbiome modulates immune checkpoint blockade efficacy in cancer. We outline diagnostic tools for dysbiosis, examine microbiota-centred interventions (e.g., faecal microbiota transplantation, probiotics, dietary changes), and propose clinical strategies. This review underscores their potential to improve ICB outcomes and reduce toxicity.

This review explores how aging alters the microvasculature and surrounding stromal cells, disrupting immune cell trafficking and promoting chronic inflammation. The authors highlight key molecular changes and propose therapeutic strategies targeting vascular aging to mitigate age-related inflammatory diseases.

Oligodendrocyte-derived IL-33 regulates self-reactive CD8⁺ T cells in CNS autoimmunity. IL-33 ablation reduces persistence and TCF-1^low effector T cell generation, mitigating disease. Local IL-33 blockade via delivery of a decoy receptor improves outcomes, highlighting tissue factors as druggable targets for chronic CNS autoimmune disorders.

Chilblains were reported in SARS-CoV-2–exposed individuals without PCR- or serologically defined COVID-19. Excessive TLR7 responses to SARS-CoV-2 by pDCs are linked to I-IFN–driven chilblain development. While TLR7 deficiency predisposes to severe COVID-19, enhanced TLR7 responses may confer sterilizing immunity to SARS-CoV-2, with chilblains as a trade-off.

Frolov et al. discover an expansion and activation of microglia and T cells preceding neuronal loss in spastic paraplegia 15, highlighting the importance of immune responses and myeloid cell–lymphocyte interactions in the pathogenesis of hereditary spastic paraplegias.

This study highlights the contribution of PRC2 to Aire-mediated stochastic gene expression and the development of mimetic cells through various single-cell approaches. The genomics data utilized in this work serve as a valuable resource for advancing research on Aire.

AIRE regulates thymic interferon-stimulated genes, preceding anti-IFNα autoantibody production in Aire-deficient rats. These autoantibodies reduce T1 IFN signaling, dampen immune activation, and correlate with lower tissue inflammation, uncovering a protective mechanism that inversely associates with autoimmune pathology.

Sandoval et al. show that a single malaria episode reprograms T cell activation to minimize cytotoxicity and injury during subsequent infections. This adaptation is long-lived, operates independently of pathogen load, and associates with immunity to severe forms of the disease.

Fike et al. describe mechanisms of IRF7-driven autoimmune B cell and autoantibody responses. Mechanistic studies guided by OMICs data reveal that IRF7 promotes lupus-prone germinal center and plasma cell responses by regulating transcriptome, translation, and metabolism of B cells.

This study identifies a balance between ILC2s and ILC3s as critical for gut tissue repair. Selective deletion experiments reveal that ILC2 loss promotes fibrosis, while ILC3 depletion protects against it, highlighting ILC3s as key drivers of intestinal fibrosis.

Nerves are integral to adenoid cystic carcinoma (ACC). We identified sympathetic nerves in ACC that promote disease progression and correlate with worse patient survival. Sympathetic nerves reflect tumor axonogenesis driven by noradrenergic neural development programs, and can be targeted as a therapeutic strategy.

Canonically, control of Mycobacterium tuberculosis infection requires a Th1 immune response and IFNγ secretion. Here, noncanonical immunity is identified as an important feature of bacterial control during tuberculosis disease when human-relevant genetic and phenotypic diversity is incorporated into model systems.

Factor XII drives thrombosis but is dispensable for hemostasis, making it an anticoagulant drug target. This study shows that factor XII–triggered coagulation traps pathogens and limits bacterial dissemination, highlighting a role of prothrombotic mechanisms in innate immunity and host defense.

Fortmann et al. unravel the immune landscape of the human choroid in health and AMD. They demonstrate that a previously unknown prenatally derived macrophage is uniquely involved in lipid metabolism and vascular maintenance and is decreased and dysfunctional in AMD.