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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.
Siliciano and colleagues describe the generation of bispecific antibodies that target the HIV-1 envelope protein (Env) on the surface of HIV-1-infected cells and the receptor CD16 on the surface of NK cells to induce the NK cell-mediated lysis of HIV-1-infected cells and reduce the viral reservoir.
Here the authors show that lithium carbonate can revitalize tumor-reactive CD8+T cells by shunting cytosolic lactic acid into the mitochondria for oxidation, indicating that lithium ions might be applied as a cancer immunotherapy.
Xue and colleagues show that the transcription cofactor Tle3 cooperates with Runx3, Tcf1 and Tbet to limit a central memory and promote an effector memory cell signature in CD8+ T cells.
Divangahi and colleagues identify a mechanism of heterologous immunity by BCG involving cross-talk between conventional memory T cells and innate memory cells against influenza A virus infection’.
Roan et al. use Olink and single‐cell RNA sequencing (scRNA-seq) to show a dysregulated crosstalk between the cellular and humoral immune responses in individuals with long COVID 8 months postinfection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Callahan et al. show that GC and extra-GC sites spawn distinct MBC subsets. MBC precursors have open chromatin regions (OCRs) that will remain open in MBC progeny, with extra-GC and GC-derived MBCs having distinct OCRs and functions.
Here the authors show that immune cell exclusion and immunosuppression in the melanoma microenviromment are driven by nerve growth factor interactions with tropomyosin receptor kinase A on melanoma cells and that a tropomyosin receptor kinase inhibitor can sensitize these tumors to immune checkpoint blockade.
Chevrier and colleagues uncovered a hierarchical cytokine circuit arising from the pairwise effects of TNF with IL-18, IFN-γ or IL-1β, which explains the organism-wide response of the host to bacterial sepsis.