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Immunological memory has long been framed through a temporal lens, defined by the persistence and rapid recall responses of antigen-experienced lymphocytes. Drawing on the neuroscience concept of the engram, I propose the immune engram as a spatial model of memory. Here, tissue-anchored, antigen-gated multicellular circuits are selectively reconstructed upon re-exposure to cognate antigen. I further outline engram tracing and circuit reprogramming as testable directions for characterizing, tracing and therapeutically reconfiguring immune memory in disease settings.
A study by Tian et al. reports that psychological stress suppresses neuronal activity in brain regions that innervate the gut, leading to intestinal dysbiosis, reduced production of spermidine and ferroptotic stress of HSCs.
A preprint by Teodoro-Castro et al. reports a nuclear role for STING in impairing DNA replication and contributing to replication stress in ageing pathologies.
A preprint by Hu et al. shows, in a mouse model of primary tauopathy, that conventional type 1 dendritic cells outside of the central nervous system prime CD8+ T cells against brain-derived antigens, which exacerbate neurodegeneration.
A preprint by Serganova, Colombo et al. shows that tumour glycolytic capacity drives vascular abnormalities that influence the response to immunotherapy.
Peripheral T cell lymphomas are aggressive cancers that frequently co-opt the signalling circuits that normally coordinate T cell activation at the immunological synapse. Here, the authors synthesize recent genomic and mechanistic evidence showing how gain-of-function lesions in TCR, co-stimulatory, and cytokine pathways, together with loss of checkpoint control such as PD1, drive malignancy.
Past failures of T cell-based vaccines for chronic viral infection may reflect suboptimal induction of quality T cell responses. Here, the authors highlight the need to integrate diverse functional attributes of T cell efficacy with the temporal and contextual demands of different viral infections. They provide mechanistic insights into the induction of CD8⁺ T cell quality to inform rational vaccine design for emerging viruses and chronic diseases such as HIV-1.
This Review discusses how cytokine multimerization affects the engagement of cytokines with their receptors and their biological activity. The authors explain the relevance of cytokine multimerization in disease settings and the implications for cytokine-targeting therapies.
This Review discusses how select metabolites and nutrients act as signalling molecules to regulate the functions of tissue-resident macrophages in obesity and metabolic disease, with effects on disease outcome.
