Designing a universal influenza vaccine must address not only viral antigenic drift but also genetic variability in human antibody responses. In this issue of Immunity, two studies from the Karlsson-Hedestam lab (Corcoran et al. and Fischer et al.) int…
The immune system is a key contributor to organismal aging. Here, Ping et al. leverage single-cell multi-omics to construct a human immune aging clock, which pinpoints T cells as an aging nexus. RUNX1 orchestrates a transcriptional network that restrai…
Inducing broadly neutralizing antibodies (bnAbs) remains a challenge in HIV vaccine development. Mishra et al. show that an engineered germline-targeting HIV trimer, Q23-APEX-GT2, primes rare V2-apex bnAb precursors in humanized mice and outbred macaqu…
The generation of immune memory is at the crux of vaccine efficacy. Here, Crotty reviews the layers of adaptive immunity—T cell, B cells, and antibodies—and their integration to generate a holistic view of vaccine response. Common misconceptions and qu…
Regulatory T (Treg) cells are phenotypically stable in inflammatory settings. Maltez et al. report that αCD40 immunotherapy induced conversion of Treg cells into FoxP3−Tbet+IFN-γ+ “ExTreg” cells within the tumor microenvironment. ExTreg cells exhibited…
Infiltration of glioblastoma (GB) cells into the brain parenchyma and colonization of distant regions are associated with disease recurrence and therapy resistance. Using 3-photon intravital microscopy in an autochthonous GB model, Nebeling et al. iden…
Aging profoundly alters memory T cell immunity, reshaping diversity, differentiation, and function. Adamo et al. review how intrinsic aging programs, antigenic experience, and tissue context shape T cell responses and discuss emerging strategies to rec…
Although long-term dietary effects on the immune system are well established, how short-term high-fat diet (HFD) alters intestinal immunity is less understood. Here, Torrico et al. show that within hours of initiating HFD, microbiota-driven inflammatio…
Variation in antibody genetics, as illustrated in the accompanying paper by Corcoran et al., can present a challenge to the development of population-wide protective vaccines. Fischer, Corcoran, et al. investigate influenza-specific antibodies to obtai…
Transcription factor RORγt is a central regulator of type 3 immunity, essential for host defense and tissue homeostasis. Fukui et al. identify a hierarchical CNS11-CNS9 enhancer cascade that governs RORγt expression across innate lymphocytes and antige…
