Category: Immunology
Early influenza virus exposure shapes the B cell response to influenza vaccination in individuals 50 years later
To understand the influence and longevity of early influenza imprinting, Spangler et al. investigate the response to an H2 HA vaccine in individuals with and without exposure to H2N2 virus 50 years ago. They find that those with prior exposure have a robust recall response of pre-existing H2-specific memory B cells established decades ago, with no detectable de novo response.
Bile acid receptor FXR promotes intestinal epithelial ferroptosis and subsequent ILC3 dysfunction in neonatal necrotizing enterocolitis
The pathogenesis of neonatal necrotizing enterocolitis (NEC) remains to be fully elucidated. Zhang et al. demonstrate that dysbiosis induces ferroptosis of intestinal epithelial cells via bile acid receptor FXR. This subsequently impairs IL-22 production by ILC3s, which drives inflammation. Inhibiting intestinal FXR or ferroptosis ameliorates NEC in the neonatal intestine.
IL-17RA signaling provides dual tumor-suppressor function during late-stage colorectal carcinogenesis
Members of the interleukin-17 family are associated with tumor progression in various settings. Denk et al. find that, in colorectal cancer, IL-17RA switches from tumor promotion during early tumorigenesis to tumor suppression during tumor invasion and metastasis. IL-17RA limits epithelial-to-mesenchymal transition and, in myeloid cells, IL-17RA stimulates IL-18 secretion to elicit anti-tumor immunity.
Integrated computational analysis identifies therapeutic targets with dual action in cancer cells and T cells
Existing cancer immunotherapy target discovery platforms typically focus on a single cell type. Luo et al. develop ICRAFT, an interactive platform that integrates CRISPR screens and transcriptomic datasets to identify immunomodulatory gene targets across multiple cell types, providing causal insights into gene perturbations and immune-related phenotypes.
Antigenic drift expands influenza viral escape pathways from recalled humoral immunity
Multiple exposures to an evolving virus can drive antibody affinity maturation toward cross-reactivity. How viruses continue to evolve despite these broad antibodies is unclear. Maurer et al. show that cross-reactive antibodies limit viral escape in the strain that elicited them, but the strain that recalled them can more readily escape.
Collaboration between interleukin-7 and -15 enables adaptation of tissue-resident and circulating memory CD8+ T cells to cytokine deficiency
Circulating memory CD8+ T cells are thought to be highly dependent on interleukin (IL)-7 signaling. Using inducible Il7ra deletion in circulating and tissue-resident memory CD8+ T cell subsets, Jarjour et al. reveal resilience to loss of IL-7 signaling and collaboration between the IL-7 and IL-15 signaling pathways.
The polyamine-regulating enzyme SSAT1 impairs tissue regulatory T cell function in chronic cutaneous inflammation
During chronic inflammation, regulatory T (Treg) cells fail to effectively control effector T cells due to unresolved mechanisms. Here, Neuwirth and Malzl et al. identify the polyamine catabolic enzyme SSAT as a key driver of Treg cell dysfunction, which is mediated through 4-1BBL interactions on keratinocytes during cutaneous inflammation.
Splenic TNF-α signaling potentiates the innate-to-adaptive transition of antiviral NK cells
NK cells possess innate and adaptive features, but unlike T and B cells, NK cells are not thought to require priming in lymphoid organs. Mujal et al. demonstrate that the spleen supports enhanced expansion of a CD69lo adaptive NK cell precursor population during MCMV infection through TNF-α-TNFR2 signaling, providing evidence for NK cell priming in the spleen.
A heart-brain-spleen axis controls cardiac remodeling to hypertensive stress
Hypertensive heart disease, initially established as an adaptive response, might progress toward heart failure, and the nervous and immune systems participate in this process, but their interaction is unclear. Perrotta et al. identify a brain-body circuit that recruits splenic PlGF to drive proliferation of NRP1+ cardiac resident macrophages and preserve cardiac function.