Browse Articles

Capturing cell organization in the tumor microenvironment using spatial proteomics can provide insight into the disease. A pair of studies applying this to advanced lung and brain tumors identifies organizational immune hallmarks that are associated with patient outcomes.

Antibody dynamics resulting from sequential immunization are complex, limiting the study of concepts such as ‘original antigenic sin’. Here, molecular fate-mapping defines an ‘addiction’ of boosted antibodies to primary clones, and OAS-like suppression of new clones, to a degree inversely related to boosting antigenic distance.

Taking advantage of intersectional genetics, Valente et al. report a novel strategy for tracking plasmacytoid dendritic cells (DCs) that enables their discrimination from conventional DCs and plasmacytoid DC–like cells, as well as transitional DCs.

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⁺ T_reg cells or IL-2⁺ T_eff cells depending on whether TGF-β disrupts TCR signaling.

Hidalgo and colleagues discuss general functional features of the neutrophil compartment that may be relevant in physiological scenarios such as specialization in naïve tissues, diversification and functional bias in inflammatory sites.

The NLRP10 protein is found to form an inflammasome complex in response to mitochondrial damage. Loss of NLRP10 from colonic epithelia promotes inflammatory bowel disease in a mouse model, while a variant predisposing to atopic dermatitis also shows loss of function.

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 (T_reg) cells during viral infection in mice that suppresses effector T cell responses and memory formation.

Marichal and colleagues use a model of niche depletion and refilling to show that engrafted Ly6C⁺ classical monocytes proliferate locally in a Csf1 receptor-dependent manner before differentiating into lung interstitial macrophages.

Cheng et al. demonstrate that an extra copy of the X-linked epigenetic regulator UTX in females increases natural killer (NK) cell effector function. As NK cells are critical for antiviral immunity, this may explain decreased severity of viral infections in females compared to males.

Dalod and colleagues utilize a combinatorial genetic reporter strategy to uniquely mark plasmacytoid dendritic cells (pDCs) in mice. They utilize these mice to identify bona fide pDCs and functionally characterize before and during viral infection, in comparison to several other DC types.