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Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8+ T cell responses.
Single-cell and spatial analyses of conserved regulatory T (Treg) cell-dependent transcriptional states of diverse accessory cell types in mouse and human lung cancer suggest rational Treg cell targeting-based combination therapy for PD-1 blockade-resistant tumors.
Schwartz and colleagues show that TH9 cells can respond to bystander cytokines IL-2 and IL-4 to induce antigen-independent expression of IL-9, promoting allergic inflammation. Il9 locus remodeling causes TH9 cell instability, preventing antigen-independent activation in individuals who are nonallergic. Therapeutic targeting of the STAT5/STAT6 activation cascade may provide relief for patients with chronic allergy.
Boyman and colleagues perform phenotypic and B cell receptor sequencing analysis of memory B cell subsets in severe acute respiratory syndrome coronavirus 2-infected and subsequently vaccinated individuals up to 1 year post-infection to show that single memory B cell clones can adopt different trajectories.
Knight and colleagues report altered granulopoiesis and increased frequency of immature neutrophil subsets with immunosuppressive properties in a subset of patients with sepsis with poor outcome.
Clarke and colleagues show that germinal center B cells have highly dynamic mitochondria, which are regulated by the transcription factor TFAM. TFAM activity is required to promote spatial entry into the germinal center reaction by modulating cellular motility.
Becher et al. perform a head-to-head comparison of multiple severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) vaccine prime-boost combinations and analyze the ensuing humoral and cellular responses in a large randomized cohort.
Immune cells are generally considered to be able to move through tissues using nonadhesive amoeboid migration mechanics. Here, the authors show that, unlike other immune cells, mast cells do not use this method and instead are completely reliant on integrin–ECM interactions.
Coukos, Corria-Osorio and colleagues use an orthogonal genetic approach to engineer CD8+ T cells into better effector synthetic cells for antitumor adoptive cell therapy. This approach generates engineered effector T cells that express an IL-2 variant, IL-33 and a programmed cell death protein 1 decoy.
In non-small cell lung cancer, the presence of monocyte-derived macrophages inversely correlates with the presence of NK cells. Merad and colleagues propose that when monocytes phagocytose tumor debris they express TREM2, become pro-tumorigenic, and suppress NK cell recruitment and activation in tumors.
CAR T cell success requires targeting tumors, but these cells can get trapped in other tissues, such as in the lungs, where they can cause pathology. Here, the authors use a loss-of-function CRISPR screen to identify regulators of CAR T cell tumor trafficking and engineer CAR T cells accordingly to overcome this limitation.
Khader and colleagues show Mycobacterium tuberculosis (Mtb)-specific B cells are needed to recruit TFH cells into follicular-like structures within lung granulomas to control the Mtb bacilli; however, specific antibodies and many conventional properties of B cells are dispensable.
APLAID is a rare autoinflammatory disorder driven by mutations in PLCG2. Here the authors provide a new mouse model using the human APLAID p.Ser707Tyr mutation. The mouse recapitulates clinical features of APLAID that can be prevented by anti-G-CSF. Individuals with APLAID were also shown to have high circulating levels of G-CSF suggesting this might be a suitable target for the clinic.
NK cells require an immunological synapse to kill cancer cells and these synapses have been shown to have membranous protrusions. Here the authors use cutting-edge imaging and other techniques to show that tumor serine metabolism results in a reduction in NK cell sphingomyelin content and a lack of these membranous protrusions, which could contribute to a failure to kill cancer cells.
Singer and colleagues show that the developmental fate of autoreactive CD4+ thymocytes is determined by the timing and duration of agonist signaling. Early agonist signaling induces clonal deletion, whereas late agonist signaling induces differentiation into Foxp3+ Treg cells or IL-2+ Teff cells depending on whether TGF-β disrupts TCR signaling.
The authors show that Nlrp10 can form a functional inflammasome in vitro and ex vivo, and that this inflammasome is protective in dextran sodium sulfate-induced colitis in mice.
NLRP10 has been considered as an inflammasome inhibitor. Here the authors show that upon mitochondrial rupture, NLRP10 assembles a canonical inflammasome and is highly expressed in differentiated keratinocytes, possibly supporting skin homeostasis.
Kamiya and colleagues examine the effects of chronic social-defeat stress on the intestinal microbiome and show a pathological role played by dectin-1 and interleukin-17 expressed by gut γδ T cells on this behavioral vulnerability.
γδ T cells contribute to cancer immunity by killing tumor cells, but their function in the context of immune checkpoint inhibition is less clear. Here the authors show that a Vδ2− subset of γδ T cells in human kidney tumors phenotypically resembles exhausted T cells yet retains this cytolytic function and can be used to predict response to immune checkpoint inhibition.
Here the authors show that unlike IL12, IFNγ can induce a T helper 1-like state in regulatory T (Treg) cells during viral infection in mice that suppresses effector T cell responses and memory formation.