Research articles

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.

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.

Lo and colleagues provide evidence for the TCR kinetic proofreading model by LAT Gly135Asp alteration to reveal functional consequences of altered kinetics in TCR activation in thymic selection and mature T-cell responses.

Zhang and colleagues perform functional, biochemical and structural analysis of a set of antibodies isolated from COVID-19 convalescents infected with wild-type SARS-CoV-2 during the first wave of the pandemic and show they have broad neutralizing activity against all SARS-CoV-2 variants tested, including omicron.

Robbiani and colleagues show that antibodies against specific chemokines are detected in COVID-19 convalescents and may modulate the inflammatory response and disease outcome.

Here, the authors show that CD8⁺ T cells egress from tumors via lymphatic vessels in a CXCL12/CXCR4-dependent manner. High-affinity antigen encounter inhibits CXCR4 and increases retention, while no encounter or weak affinity directs T cell exit to limit local tumor control.

Unlike metabolic reprogramming that is characteristic of macrophage inflammatory polarization responses to lipopolysaccharide and TLR4 stimulation, the metabolism underlying inflammatory responses to CD40 signaling is not well characterized. Here the authors show CD40 signaling drives fatty acid oxidation and glutamine metabolism resulting in regulation of the NAD⁺/NADH ratio, which in turn promotes antitumor and pro-inflammatory macrophage functions.

Type 1 diabetes is associated with homozygous expression of specific major histocompatibility complex class II beta chain polymorphisms. Here the authors show that the disease-protective effect of major histocompatibility complex class II heterozygosity is conferred by non-cognate thymocyte negative selection.

Benhar and colleagues provide an atlas of non-neuronal cells in the adult mouse retina at steady state and after optic nerve injury and identify key cellular and molecular events along the path of neuronal degeneration after injury.

Here, the authors show that acute influenza infection induces trained immunity in self-sustaining resident alveolar macrophages, which independently exert long-term antimetastatic immune surveillance in the lung via enhanced tumor killing.

Here the authors show that dihydroorotate dehydrogenase in the de novo pyrimidine synthesis pathway functions as a cell fate checkpoint that can be targeted to specifically diminish the number and function of effector T cells without affecting the memory T cell pool and response to infection.