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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 (Treg cells) secrete IL-27 under inflammatory conditions, allowing them to selectively limit intestinal helper T17 cell (TH17 cell) responses in various disease settings.
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.
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.
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.
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.
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.
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.
Regulatory T (Treg) cells maintain the balance between immune protection and pathology. Research has now found that intestinal Treg cells produce IL-27 to restrain TH17 cell-mediated immune responses, effectively restricting autoimmune inflammation and limiting T cell responses to certain gut pathogens.
Regulatory T (Treg) cells are functionally heterogeneous, yet how each Treg cell subset exerts its suppressor function remains unresolved. Lin et al. identify IL-27 as a key Treg cell effector molecule selectively required for gut TH17 cell regulation.
Minguet and colleagues systematically examine how individual CD3 chains of the TCR–CD3 complex can improve chimeric antigen receptor (CAR) T cell performance.
Mathis and colleagues identify a subset of muscle mesenchymal stromal cells that coordinates tissue immune responses and drives regenerative mechanisms following muscle injury.
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.
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.
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.
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.
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.
Severe COVID-19 is marked by excessive inflammation that can persist after infection. The commensal yeast Candida albicans is now implicated in the acute and chronic immunopathology of COVID-19.
Iliev et al. report that increased Candida albicans accumulation in the mycobiota of patients with severe COVID-19 might be a contributing factor to the immunopathology of severe COVID-19 and have long-lasting effects on the hematopoietic stem cell compartment.