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Yaoyuan Zhang et al.
Zhang et al. reveal a role for hypomorphic SH2B3 in lupus risk. The study shows that rare, damaging variants in lupus patients enable breach of B cell immune tolerance checkpoints and suggests involvement for dysregulated IL-4R signaling and BAFF-R expression.
Article
Mathilde Ruggiu et al.
The peripheral activity of anti-PD-1 mAb is not fully understood. Here, Ruggiu, Guérin et al. demonstrate that anti-PD-1 mAb promotes CD8+ T cell responses in tumor-draining lymph node by targeting Tfh cells and stimulating IL-4 production.
Technical Advances and Resources
Lauren E. Milling et al.
Milling et al. report an experimental and analytical framework for performing in vivo CRISPR screens in immune cells. As a proof-of-concept, they demonstrate the utility of incorporating unique molecular identifiers into CRISPR screen libraries for improving statistical power and tracking clonal dynamics. Briefly, log2-normalized gRNA count tables for input, replicate pools of mice from the tumor, and replicate pools of mice from the tdLN were created as above. TdLN versus input, tumor versus input, and tdLN versus tumor fold changes were calculated, as above, for replicate mouse pools A–F. The Pearson correlation coefficient was calculated for all pairwise combinations of A–F for a given comparison (tdLN versus input, tumor versus input, or tdLN versus tumor). Each pairwise combination is indicated by an individual square in the heatmap.
Article
Gengyi Zou et al.
This research dissects diffuse-type gastric adenocarcinoma (DGAC), an aggressive and therapy-resistant cancer, and unveils that CDH1/E-cadherin inactivation is associated with EZH2 activation and a distinct tumor immune profile, proposing a new molecular subtype of DGAC.
Article
Kellen J. Cavagnero et al.
Cavagnero et al. use single-cell transcriptomics to identify dermal immune acting fibroblast (IAF) subsets that communicate with neutrophils during type 17 inflammation. Fibroblast-specific deletion of Il17ra in mice and analysis of human skin following anti–IL-17 demonstrate that such CXCL12+ IAFs play an important role in neutrophil recruitment.
Article
Rina Matsuda et al.
Monocytes restrict Yersinia infection within intestinal pyogranulomas. Here, we report that monocyte-intrinsic TNF signaling drives the production of IL-1 that signals non-hematopoietic cells to control intestinal Yersinia infection within pyogranulomas.
Brief Definitive Report
Mariah Hassert et al.
Lung resident memory CD8+ T cells (TRM) control heterosubtypic influenza infection and potentially cancer. We show that thorax-targeted irradiation depletes lung TRM and diminishes protection, but spares circulating memory CD8+ T cells that can be boosted to regenerate lung TRM.
Issue Cover
Current Issue
Volume 221,
Issue 2,
5 February 2024
Reviews & Opinions
Review
Jana L. Raynor, Hongbo Chi
Nutrients interplay with Signal 1 (antigens), Signal 2 (co-stimulation), and Signal 3 (cytokines) to orchestrate T cell activation, differentiation, and function. This review highlights the signaling and functional effects of nutrients as Signal 4 in T cell–mediated immunity.
People & Ideas
Lucie Van Emmenis
Rita Colwell is a Distinguished University Professor at the University of Maryland at College Park and at Johns Hopkins University Bloomberg School of Public Health, and president of the Rosalind Franklin Society. She has authored or co-authored 20 books and more than 800 scientific publications, and throughout her career has focused on improving health outcomes across the world and highlighting the impacts of infectious diseases in drinking/bathing water. We recently spoke to Rita about her career and her thoughts about the future for women in science.
Review
Maurice Reimann et al.
Cellular senescence is a stress-inducible terminal cell-cycle arrest program with far-reaching pathophysiologic implications. This Review summarizes the evidence that senescent cells need to actively maintain their arrest machinery and discusses the consequences if these epigenome-remodeled cells resume proliferation in a “post-senescent” condition.

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