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Issues

Perspective

In Special Collection: Innate Lymphoid Cells 2024

NK cells were first described five decades ago and named in 1975. This brief Perspective highlights a timeline of a few selected advancements in NK cell biology in each decade from a personal perspective of being involved in this quest.

Article

This study uncovers that the CV-A10 virus contributes to onychomadesis in hand-foot-and-mouth disease by inhibiting Wnt/β-catenin signaling through KRM1 receptor invasion. It highlights the activation of the Wnt pathway as a potential treatment and offers novel insights into virus–host cellular signaling interactions.

The guard protein NLRP1 senses pathogen-encoded effector activities, but whether successful pathogens evade the consequences of NLRP1 activation is less clear. Parameswaran et al. demonstrate that HSV-1 inhibits the antiviral NLRP1 pathway via production of a viral E3 ubiquitin ligase.

In Special Collection: Innate Lymphoid Cells 2024

Mathä et al. report a resting CD127CD45RO+ ILC2 population in humans that exhibits features of memory cells. These memory ILC2s are present in the circulation and tissues of healthy individuals and patients with chronic type 2 inflammation.

This work reports a mutagenesis screen of the TLR chaperone protein UNC93B1 that reveals regulatory regions affecting TLR3, TLR7, and TLR9 responses. Autoimmune patients are identified with coding variants in UNC93B1 that map to regions identified by the screen, and the introduction of these human variants into mice leads to TLR-driven autoimmune disease.

STAT3 gain-of-function syndrome causes early-onset autoimmunity and immune dysregulation in patients. Here, we report spontaneous and stimulus-driven skin disease in a mouse model associated with locally increased Th17 that is partially dependent on IL-22 signaling.

This study analyzes persistent germinal center (GC) reactions in two individuals vaccinated with the inactivated, cell line–derived seasonal influenza vaccine. These sustained GC reactions support the maturation of responding B cells by enhancing their binding affinity and breadth.

Brief Definitive Report

In Special Collection: JEM Mucosal Immunology 2024

IL-6–dependent Th17-to-Tfh plasticity during periodontitis limits disease pathology. Loss of Th17-to-Tfh cells results in altered oral antibody production and increased biomass of the oral microbial community. Our data demonstrate that Th17-to-Tfh plasticity reinforces gingival barrier integrity during inflammation.

David et al. describe UNC93B1 missense substitutions causing systemic lupus erythematosus or chilblain lupus, inherited as either autosomal dominant or autosomal recessive traits. In vitro and ex vivo assays show that these variants confer differential hypermorphic TLR7 and TLR8 signaling.

Ding and Hagan et al. discover a unique requirement for Ki67 in regulating chromatin accessibility in the early stages of lymphocyte development undergoing V(D)J rearrangement, thus ensuring normal immunoglobulin gene recombination, cell maturation, and peripheral representation.

Technical Advances and Resources

Tran et al. use single-cell RNA-sequencing to discover diverse immune cell populations in bladder cancer patient urine that have highly similar gene expression programs to those in tumor.

Insights

In this issue, two studies report the analysis of seven patient variants combined with a comprehensive alanine screen and reveal that different regions of UNC93B1 selectively regulate different TLRs.

Germline activating mutations in STAT3 cause a multi-systemic autoimmune and autoinflammatory condition. By studying a mouse model, Toth et al. propose a role for dysregulated IL-22 production by Th17 cells in causing some aspects of immune-mediated skin inflammation in human STAT3 GOF syndrome.

Found in Translation

Cancer Focus

Recent studies suggest that personalized cellular therapies using T cells transduced with private TCRs hold the potential to transform the field and provide new treatment options for cancer patients, reflecting significant analogies with the evolution of cancer vaccines toward personalization.

Viewpoint

This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.

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