Issues

Xu et al. define NAD-induced cell death via purinergic P2RX7 receptor in type 1 unconventional T cells, particularly intrahepatic MAIT cells that are pivotal in liver homeostasis. Therefore, P2RX7 is a potential target to modulate unconventional T cells in immunopathological conditions and cancer.

Schuijs et al. highlight a novel role for basophils during allergic immune responses to house dust mites (HDM), revealing how interleukin-33 (IL-33)-activated basophils facilitate recruitment and extravasation of Th2 cells into the lungs.

ITGAV-containing integrins play a unique role in activating the cytokine TGF-β. Whole exome sequencing in IBD patients revealed variants of ITGAV that impaired integrin function, including downstream TGF-β signaling, as determined in patient cells and modeled in zebrafish.

Infections with arboviruses Powassan virus (POWV), Usutu virus (USUV), or Ross River virus (RRV) are rare but can cause severe disease. We report autoantibodies neutralizing type I IFNs in patients with POWV encephalitis, severe USUV infection, and severe RRV infection.

Xu et al. reveal that the ARTC2–P2RX7 regulatory axis is a key modulator of unconventional T-cell survival. Their findings show how this pathway selectively influences innate-like, IFN-γ and IL-4 co-producing T cells, providing insights into immune regulation during tissue damage.

The role of basophils in asthma is unclear. Here, Schuys and Brenis et al. show that they control the extravasation of pathogenic effector Th2 cells into the lungs. Basophils are activated by IL-33 to produce IL-4, which primes lung endothelium.

Tejedor Vaquero et al. show that gut IgA1 and IgA2 subclasses co-emerge early in life, largely derive from clonally related and somatically mutated plasma cells in adults, and show unique changes of both frequency and reactivity in inflammatory bowel disease.

The gut commensal protist Tritrichomonas musculis (T.mu) boosts T cell–dependent IgA. T.mu-driven IgA modifies the commensal bacterial microbiota and improves the generation and dissemination of IgA-secreting plasma cells reactive against orally ingested food antigens.

Shi et al. use forward genetics and identify a null allele of H2-Aa that enhances cDC2 cross-priming of CD8 T cells, enabling mice to suppress malignant melanoma growth. This work suggests host MHC-II as a potential target for cancer immunotherapy.

Dampened antigen presentation is critical for cancer immune evasion and a major hurdle for immunotherapy. The study by Yu and colleagues uncovers MCRS1 as a new activator of major histocompatibility complex (MHC) class I, which elicits anti-tumor immunity and enhances anti-PD-1 therapy.

Murphy and Miyamoto et al. have developed a non-T cell targeting immune therapy for metastatic ovarian cancer. This approach induces tumor regression by activating antitumor immunity, capturing disseminating cells in the peritoneal fluid, and expanding IL27+ macrophages in the omentum.

Bellos et al. identify an enrichment of rare, damaging variants in BTNL8 in MIS-C patients. These variants result in impaired Vγ4⁺ γδ T cell engagement associated with altered gut homeostasis, which may contribute to the pathogenesis of MIS-C.