Volume 24 Issue 12, December 2023

The immune response to dengue virus infection is a well-coordinated balancing act. New research shows that an imbalanced response — driven partially by the productive infection of antigen-presenting cells — is associated with progression to severe disease.

S100A8 and S100A9 are cytosolic alarmins with autocrine functions that facilitate neutrophil recruitment. Rapid, transient gasdermin-D pore formation is now shown to mediate secretion of these proteins in response to E-selectin without driving pyroptosis.

Regulatory T (T_reg) cells maintain the balance between immune protection and pathology. Research has now found that intestinal T_reg cells produce IL-27 to restrain T_H17 cell-mediated immune responses, effectively restricting autoimmune inflammation and limiting T cell responses to certain gut pathogens.

Determining the immune crosstalk between macrophages and NK cells in bronchioalveolar lavage fluid during SARS-CoV-2 infection in macaques identifies immunoregulatory properties of NK cells and their implications for viral persistence.

After acute injury to skeletal muscle, an ‘early responder’ subtype of stromal cells rapidly produces an array of inflammatory mediators. Disruption of this response causes abnormal accumulation of several adaptive lymphocyte populations, a prolongation of inflammation, and an effect on tissue regeneration.

Cancer cells often overexpress CD47, which triggers the macrophage receptor SIRPα to elude anti-tumor immunity. We found that CD47 also suppresses phagocytosis by masking a pro-phagocytic ligand, SLAMF7, on tumor cells. We generated a first-in-class SLAMF7 antibody, which dissociated the CD47–SLAMF7 cis interaction, enabling anti-tumor immunity during SIRPα blockade.

Interleukin-27 (IL-27) is a pleiotropic cytokine known for its diverse immune regulatory properties. Although innate immune cells are considered the major cellular sources of IL-27, we found that gut regulatory T cells (T_reg cells) secrete IL-27 under inflammatory conditions, allowing them to selectively limit intestinal helper T17 cell (T_H17 cell) responses in various disease settings.

We are in the midst of an explosion of multiomics and spatial data along with constant innovation of the tools used to study these data. In this Review article, as part of our Cancer Immunology and Immunotherapy series, the authors discuss these innovations and their application to study the tumor microenvironment.

Here the authors review CAR T cell engineering and immunotherapy for cancer and juxtapose state-of-the-art developments with CAR NK cells as part of our Cancer Immunology series of Reviews.

Bantug and Hess discuss the metabolic interplay between tumor-resident cells and how the effect of metabolism-targeted anticancer strategies on non-transformed or immune cells in the tumor needs to be considered.

Neutrophils can release S100A8/S100A9 as an alarmin via gasdermin D pores. Here, the authors untangle the regulatory mechanisms driving this pathway and show that active repair processes make these pores transient, which can prevent the usual lytic cell death.

Veillette and colleagues show that CD47 on tumor cells interacts in cis with the pro-phagocytic ligand SLAMF7, masking the ability of SLAMF7 to engage its homotypic receptor on macrophages and to trigger phagocytosis.

Individuals with advanced cancers can develop thrombocytosis and anemia. Huang and colleagues show that in tumor-bearing individuals, increased circulating kynurenine results in megakaryocyte differentiation from megakaryocytic–erythroid progenitor cells by activating the aryl hydrocarbon receptor, resulting in increased expression of RUNX1.

Mathis and colleagues identify a subset of muscle mesenchymal stromal cells that coordinates tissue immune responses and drives regenerative mechanisms following muscle injury.

Huot et al. show that interferon-γ (IFN-γ) regulates the persistence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in bronchoalveolar macrophages from cynomolgus macaques up to 18 months postinfection.

Iwawura et al. identify a noncanonical role for NOD1, independent from its CARD-mediated proteoglycan sensing. Interactions between NOD1 and STAT5 are required for optimal lymphopoiesis in response to homeostatic cytokines.

Luster and colleagues report that lung-resident ST2⁺ regulatory T cells secrete the IL-1 antagonist IL-1Ra to suppress neutrophils and early innate immune responses to influenza virus infection.

Regulatory T (T_reg) cells are functionally heterogeneous, yet how each T_reg cell subset exerts its suppressor function remains unresolved. Lin et al. identify IL-27 as a key T_reg cell effector molecule selectively required for gut T_H17 cell regulation.

Love and colleagues find an inhibitory function for CD3ζ ITAMs in response to low-affinity ligands, meaning that CD3ζ can perform a dual function in TCR signaling by playing a positive or negative role depending on the affinity of the TCR for its peptide ligand.

Minguet and colleagues systematically examine how individual CD3 chains of the TCR–CD3 complex can improve chimeric antigen receptor (CAR) T cell performance.

Einav and colleagues characterize peripheral immune blood cells from pediatric patients with severe natural dengue infections. Their findings suggest that disease progression is associated with an inflammatory phenotype accompanied by impaired interferon response, defective antigen presentation and regulation of effector lymphocyte responses.