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  • The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.

    • Qian Liu
    • Thames Pickett
    • Barbara Rehermann
    Meeting Report
  • How aging, immunity and cancer are related is incompletely understood. Data now show altered differentiation and loss of function of tumor-infiltrating T cells with aging. So-called TTAD cells seem to be involved.

    • Justin E. Wilson
    • Janko Ž. Nikolich
    News & Views
  • Cancer and aging are associated with each other, but underlying mechanisms contributing to this correlation are unclear. Here the authors identify a dysfunctional T cell state that is distinct from typical T cell exhaustion and only occurs in the tumor microenvironment during later life.

    • Alex C. Y. Chen
    • Sneha Jaiswal
    • Debattama R. Sen
  • Our work identifies previously unrecognized functional heterogeneity in tissue-resident interstitial macrophages. We have identified ten macrophage subsets, each thought to specifically contribute to recruiting and organizing cell types within tissues. Moreover, our findings suggest the diversity and division of labor extend to other macrophage populations previously considered homogeneous.

    Research Briefing
  • Singh and colleagues show Tigit controls the generation of germinal center-derived plasma cell precursors that give rise to long-lived differentiated progeny in the bone marrow.

    • Godhev Kumar Manakkat Vijay
    • Ming Zhou
    • Harinder Singh
  • In this Review, the authors analyze evidence for autoimmunity against components of antimicrobial immunity, metaphorically represented by the mythical ouroboros snake eating its own tail.

    • Jean-Laurent Casanova
    • Jessica Peel
    • Paul Bastard
    Review Article
  • Homeostatic immune cells remain perpetually vigilant against pathogens. We found that baseline JAK–STAT signaling supports the characteristic transcriptional and epigenetic state of homeostatic T cells and macrophages in mice. JAK–STAT signaling under homeostatic conditions was driven by signals from healthy tissue and did not require external immune stimuli.

    Research Briefing
  • We report two patients with biallelic SHARPIN deficiency, which manifests with autoinflammation and B cell immunodeficiency and is phenotypically distinct from Sharpin deficiency in mice. In one patient, there was a significant shift from pro-survival signaling to cell-death signaling in fibroblasts and lymphoblasts induced by members of the TNF cytokine superfamily, accounting for the autoinflammation and immunodeficiency. Targeted therapy with TNF inhibitors had a dramatic beneficial effect.

    Research Briefing
  • The microbiome is known to affect antitumor immune responses, but how this occurs is unclear. Rhamnose-rich polysaccharides (RHP) from a commensal strain of Lactiplantibacillus plantarum have now been shown to induce iron sequestration by tumor macrophages, thereby limiting tumor growth and promoting antitumor immunity.

    • Samuel P. Nobs
    • Eran Elinav
    News & Views
  • Bock and colleagues perform integrative analysis of JAK-STAT mutant mice and find JAK-STAT signaling regulates CD8+ T cell and macrophage homeostasis by contributing to a poised epigenetic and transcription-regulatory state, preparing cells to rapidly respond to stimuli.

    • Nikolaus Fortelny
    • Matthias Farlik
    • Christoph Bock
    ArticleOpen Access