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Koh et al. show that loci active in differentiated effector T cells are poised in early T precursors before the expression of T cell antigen receptors in a manner dependent on the chromatin remodeling complex mammalian SWItch/Sucrose Non-Fermentable and the PU.1–RUNX1 and BCL11B–RUNX1 complexes.
Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.
Cupedo and colleagues show that neutrophils promote a tumor-supportive microenvironment via a self-amplifying interaction between neutrophils and bone marrow stromal cells. This scenario creates a promyeloma niche that is difficult to treat despite targeted therapies directed at the myeloma cells.
Here the authors identify the transcription factor MEF2C as essential for human NK cell function and viral immunity in mice and humans. This control is exerted via regulation of lipid metabolism, and deficiency in MEF2C can be overcome by oleic acid supplementation.
CD103+ T cells are associated with control over tumors but how this is mediated is unclear. Here the authors show that CD61 colocalizes and functionally combines with CD103 in the T cell synaptic response to promote antitumor T cell responses.
Here the authors show a mechanism by which mitochondrial electron transport and ROS contribute to the differentiation and function of regulatory B cells in the context of systemic lupus erythematosus.
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.
Abraham and colleagues found that antigen-triggered degranulation in IgE-sensitized mast cells was mediated by the inflammasome components NLRP3 and ASC.
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.
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.
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.
Smith and colleagues find that a multivariate signature of unresolved inflammation and altered iron homeostasis detected beyond 2 weeks following acute COVID-19 onset was the strongest early differentiator of those who report long COVID symptoms at 3–10 months.
Linnerbauer and colleagues find that HB-EGF produced by reactive astrocytes is protective during autoimmune neuroinflammation, but epigenetically suppressed during late stages.
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.
IL-23 promotes tumor growth in preclinical cancer models and correlates with adverse clinical outcomes. Here, Becher and colleagues find that IL-23 produced by tumor-associated macrophages stabilizes Treg cell identity, promoting immunosuppression and tumor growth.
Here, the authors target intratumoral Treg cells to enhance antitumor immunity without affecting systemic Treg cell function and identify JMJD1C as a critical epigenetic regulator of tumor Treg cell fitness.
Here, the authors characterize two distinct Treg cell populations in the visceral adipose tissue of lean and high-fat diet-fed mice. ST2+ Treg cells are dominant in male mice and are transcriptionally driven by GATA3 and PPARγ, regulators that limit the differentiation of the more female-dominant population of CXCR3+ Treg cells that are T-bet dependent. Functional distinctions are also evident in glucose tolerance and adipose inflammation.
Reis e Sousa et al. show that cDC2As and cDC2Bs are derived from distinct subsets of bone marrow pre-cDC2s, suggesting that the two lineages are ontogenetically determined.
Here, the authors enhance their nasally delivered chimpanzee adenoviral-vectored SARS-CoV-2 vaccine with an Omicron-matched vaccine (ChAd-SARS-CoV-2-BA.5-S) that stimulates mucosal immunity in mice and hamsters and shows cross-reactive CD8+ memory T cell-driven protection against antigenically distant strains.