Volume 25 Issue 4, April 2024

Granulosomes are novel complexes that feature an unexpected partnership between the tetraspanin CD63 and the inflammasome proteins NLRP3 and ASC. Granulosomes assemble on mast cell granules to propel them along microtubules to the plasma membrane for degranulation.

Profiling of plasma proteins in individuals with COVID-19 shows that complement activation and myeloid inflammation are major pathways in the pathogenesis of long COVID and identifies distinct profiles of immune dysregulation in individuals with long COVID, highlighting the heterogeneous and diverse nature of this disease.

Understanding normal hematopoiesis is critical to understanding disease. Technological advances are driving insight into human hematopoiesis at unprecedented resolution. Integrating ‘-omics’ datasets with machine learning has yielded a high-resolution map of primary human bone marrow hematopoietic progenitor cells that supports the study of immune cell development, as well as the origins of disease.

DNA sensing for the purposes of innate immunity is tricky when the DNA sensor can easily become stuck on chromosomes during cell division. The mechanism by which the trapped DNA sensor is degraded — and how this process can be balanced with added immune protection — is now reported.

T cell- and antibody-based immunological protection are generally considered to function together, but data now show how T cells conferred by previous SARS-CoV-2 infection or two-dose vaccination can elicit heterologous protection in mice against subsequent SARS-CoV-2 infection, even in the absence of antibodies.

Autoantibodies that develop in systemic lupus erythematosus (SLE) can cause long-term cognitive impairment that remains even after the systemic disease becomes quiescent. This study attributes the persistent cognitive symptoms of SLE to a self-sustaining neuroinflammatory process that continues indefinitely unless disrupted — which can be done using medications approved by the US Food and Drug Administration.

In this Review, Kim et al. provide an overview of the prenatal immune conditions that contribute to the development of neurodevelopmental disorders and the immunological signatures and disorders associated with neurodevelopmental disorders.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

Zhang and colleagues found that Omicron RBD binding to Siglec-9 impaired phagocytosis and antigen presentation in macrophages, an effect abrogated by an F375S mutation in the spike protein of Omicron.

Here the authors use three different mouse models to show that prior infection or mRNA vaccination can protect against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) independently of antibodies, highlighting the importance of T cell-derived interferon-γ (IFN-γ) in host defense and the need to consider this measure of protection in vaccination.

The spatial organization of cells in solid tumors is considered to be important for immune response and response to therapy. Here the authors use multiomics including spatial transcriptomics of human lung tumors prior to patients being treated and show among other things an association of stem-immunity hubs rich in stem-like CD8⁺ T cells with positive response to anti-PD-1 therapy.

Here the authors present a method they call CM-Drug for the identification of combination drugs that can boost the efficacy of immune checkpoint blockade therapy. They validate this method with melanoma and lung cancer models in mice and explore in further depth one hit from their screen, the thyrotropin-releasing hormone (TRH) analog taltirelin.

Systemic lupus erythematosus is associated with neurological impairment. Here the authors show that exposure of hippocampal neurons to lupus autoantibodies in mice initiates a neuroinflammatory state sustained by continuous HMGB1:RAGE signaling that can be reversed with an ACE inhibitor.

Here the authors use positron emission tomography to visualize fibroblasts in patients with arthritis and combined with spatial transcriptomic data show that these cells undergo a phenotypic shift upon resolution of inflammation. A CD200⁺DKK3⁺ fibroblast subset promotes this resolution by inhibiting tumor necrosis factor and interleukin-17A.

Abraham and colleagues found that antigen-triggered degranulation in IgE-sensitized mast cells was mediated by the inflammasome components NLRP3 and ASC.

In this Resource article, the authors integrate genomic, bioinformatic and flow cytometric data from human bone marrow to provide an atlas of hematopoietic progenitor cell states in health and disease.