The mechanisms linking defective protein prenylation to systemic inflammation in mevalonate kinase deficiency remain unclear. Munoz et al. reveal that mice and humans with MKD have defective NK cells, with impaired granule trafficking, reduced cytotoxi…
CD8+ T cells must retain functional resilience as they traverse diverse environments. Scaglione et al. reveal how the integrated stress response enables CD8+ T cells to engage alternate biosynthetic modes under environmental stress that prevent dysfunc…
Ulezko Antonova et al. examine plasmacytoid dendritic cells (pDCs) in lymphoid tissues from infancy to adulthood and identify a cycling population of pDCs in fetal and infant lymphoid organs that is found only in the bone marrow in adults. pDCs in sepa…
Geng et al. identify KLF2 as a central regulator of CX3CR1+ effector-like exhausted CD8+ T cells during chronic infection. KLF2 is uniquely expressed and both necessary and sufficient for this state. Disrupting the KLF2-dependent program enhances viral…
Tumor-associated macrophages (TAMs) can limit anti-tumor immunity. Sun et al. find that SPP1+ TAMs are enriched in tumors across cancer types and associated with resistance to immune checkpoint blockade. Mechanistically, SPP1 interacts with TRIM21 to l…
Advancements in human genetics have catalyzed rapid discovery in immunology. Graham and Xavier review how functional genomics and chemical biology have joined forces to uncover mechanisms of mucosal immunity and the pathophysiology of inflammatory bowe…
Therapeutic monoclonal antibodies are central to cancer treatment but often show incomplete efficacy. Cheng et al. demonstrate that transient host-cell glycoengineering to reduce N-glycan trimming strengthens IgG-FcγRIIIa bond resilience under vascular…
Pre-metastatic niche formation is a pivotal driver of breast cancer lung metastasis; however, the mechanisms underlying changes in vascular endothelial permeability remain unclear. Qian et al. demonstrate that triple-negative breast cancer-induced palm…
TREX1, but not other DEDDh exonucleases, restrains cGAS-STING activation by cytosolic DNA. Zhu et al. examine the basis for this specificity and define a modular double-stranded DNA (dsDNA)-recognition architecture within TREX1 comprising R128, a subst…
Specialized fibroblastic reticular cell (FRC) subsets in lymph nodes orchestrate the compartmentalization that guides immune cell migration, interaction, and function. Alouche et al. examine the signals governing FRC differentiation and identify a Notc…
