Research Briefing

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  • Intestinal group 3 innate lymphoid (ILC3) cells exhibit increased mobility in response to flagellin-mediated inflammation. This ‘patrolling’ behavior promotes IL-22 diffusion and prevents intestinal epithelial cell death. Enhanced ILC3 dynamics rely on environmental cues and suggest a prominent ILC3 tissue adaptation that reinforces intestinal barrier integrity.

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  • Tissue-destructive fibroblasts in arthritis are driven by the transcription factor ETS1. Analysis of a cross-tissue, single-cell fibroblast dataset and genetic loss-of-function approaches further suggest that ETS1-expressing fibroblasts have a universal role in pathological tissue remodeling in multiple diseases, including arthritis, colitis and cancer.

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  • Deacetylation of specific lysine residues in the DNA-binding domain of the transcription factors IRF3 and IRF7 by SIRT1 is necessary for liquid–liquid phase separation and transactivation of type I interferons. SIRT1 agonists partially restored the impaired innate immune responses in senescent cells and aged mice, suggestive of a possible strategy for preventing innate immunosenescence.

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  • The response of circulating effector CD4 T cells to type I interferons (IFN-I) correlates with the overall survival of patients with cancer receiving immune checkpoint inhibition. IFN-I responsiveness is already epigenetically encoded before treatment initiation, highlighting a deterministic, clinically relevant feature that can predict therapeutic efficacy.

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  • Crystal structures of the immune checkpoint protein LAG3 reveal critical binding interfaces for inhibitory antibodies and cellular ligands, such as FGL1 and MHC class II molecules. These structures provide insight into the dimeric assembly of LAG3 proteins on the surface of T cells and suggest FGL1-induced clustering as an immunomodulatory mechanism.

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  • A single-cell sequencing study shows that the human memory B cell repertoire is dominated by large IgM, IgG2 and IgA immunoglobulin families, whereas IgG1 families, including those specific for recall antigens, are of a small size. Multi-year analysis shows that memory B cell families are highly stable and that plasmablasts of T cell–independent and T cell–dependent isotypes are produced in a recurrent manner.

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  • Using high-resolution molecular and optical mapping of the three-dimensional genome, we found that the transcription factor TCF-1 is linked to changes in the structure of topologically associating domains in T cell progenitors that lead to interactions between previously insulated regulatory elements and target genes at late stages of T cell development.

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  • This study shows that systemic hypoxia alters the response of the bone marrow to inflammation by reducing type I interferon signaling and suppressing the accumulation of monocyte-derived macrophages in the lung. These events, in turn, hinder the resolution of lung inflammation.

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  • Intra-islet CD8+ T cells from a mouse model of type 1 diabetes exhibit an exhausted phenotype that differs from the canonical T cell exhaustion observed in cancer and chronic viral infection. Deletion of the inhibitory receptor LAG3 in these cells accelerated diabetes incidence and partially reversed this restrained phenotype.

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  • Using a gene-delivery system, we show that ectopic expression of interleukin 2 (IL-2) within reactive astrocytes stimulates brain-specific expansion of resident regulatory T cells. Such gene delivery protects against neuroinflammation in several mouse models of disease and injury, with potential implications for patients with traumatic brain injuries.

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  • Switching the CD4 and CD8 coreceptor proteins encoded in Cd4 and Cd8 loci results in a reversed T cell immune system, with CD4+ cytotoxic T cells and CD8+ helper T cells. Thus, whichever coreceptor is encoded in Cd4 promotes a helper lineage fate, and whichever is encoded in Cd8 promotes a cytotoxic lineage fate.

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  • A new genetic ‘recorder’ of long-term cell proliferation revealed substantial heterogeneity in the division history of central memory CD8+ T cells. Importantly, the extent of past proliferation was related to distinct transcriptional features and re-expansion potential, highlighting an unappreciated division of labor within the central memory T cell pool.

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  • Systemic inflammatory responses generated by lipid-formulated RNA vaccines are driven by differential induction of pro- and anti-inflammatory interleukin-1 (IL-1) family members in mice and humans. Whereas RNA modifications can prevent these pro-inflammatory responses, certain lipid formulations used in the vaccines can induce IL-1-mediated innate immunity even in the absence of RNA.

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  • Alveolar macrophages (AMs), the resident macrophages of the lung, can be expanded ex vivo to generate large numbers of cells but show culture adaptations related to epigenetic and transcriptional changes. After transplantation into the lungs of mice, however, culture-expanded AMs lose these adaptations, fully restore in vivo identity and functionally reconstitute the AM pool.

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  • Coronavirus-specific antibody and T cell responses were characterized in young children who had been naturally infected with SARS-CoV-2. Immune responses were focused against the spike protein, strong and stable in magnitude, and showed notable cross-reactivity with other human coronaviruses.

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  • Mitochondria regulate endoplasmic reticulum (ER) size and protein maturation in healthy cells by releasing aspartate, regenerating cytoplasmic NAD+ and ADP-ribosylating the ER stress sensor BiP. In the autoimmune disease rheumatoid arthritis, a deficiency in mitochondrial aspartate in T cells causes an increase in ER size and excess production of the inflammatory mediator tumor necrosis factor (TNF), driving tissue inflammation.

    Research Briefing