Volume 24 Issue 4, April 2023

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.

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.

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.

Several panels of naturally arising antibodies against specific chemokines are closely correlated with various favorable COVID-19 outcomes, raising an opportunity to target the chemokine system for long COVID treatment.

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.

Homozygous expression of MHC-II alleles that confer susceptibility to type 1 diabetes limits the efficiency of thymic negative selection and allows for CXCR6⁺ pathogenic clones to orchestrate the disease process. Expression of a second MHC-II allele decreases β-islet CD4⁺ T cell affinity, and limits CD8 cross-priming and diabetes risk without presenting the cognate MHC-II islet self-antigen.

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 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.

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

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.

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.

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.

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.

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.

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.

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.

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.