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Insights

Folkert et al. define an “iron-rich” subset of tumor-associated macrophages (iTAMs). The metabolism of heme leads to the degradation of the transcriptional repressor Bach1 and shapes the transcriptional profile of iTAMs. The endothelin receptor B in iTAMs signals tumor-supportive functions.

Viewpoint

Juliane Bubeck Wardenburg and Stephanie A. Fritz explore the biological linkage between microbial niche acquisition and host immunity as a basis to guide future vaccine efforts against Staphylococcus aureus infection.

Reviews

Thymus and T Cell Development Focus
In Special Collection: Autoimmunity 2024

Multipotent blood progenitors begin T cell development in the thymus, activating a multistep gene regulatory network. This review explores how the dynamic interplay between Notch signals, Notch-induced factors, and progenitor-associated factors control T-development progression by synergizing and opposing each other’s action.

Thymus and T Cell Development Focus
In Special Collection: Autoimmunity 2024

TCR rearrangement endows the preselection thymocyte repertoire with wide-ranging ligand specificity. Here, we discuss how thymic selection matures or eliminates clonotypes with particular specificities and develops T cell sublineages and microrepertoires according to their antigen-recognition capabilities.

Thymus and T Cell Development Focus
In Special Collection: Autoimmunity 2024

This review covers recent advances in our understanding of how developing T cells sense and adjust to their self-reactivity and how this impacts their decision to become a CD8 T cell, a CD4 T cell, or a regulatory T cell.

Thymus and T Cell Development Focus
In Special Collection: Autoimmunity 2024

Thymic epithelial cells (TECs) are essential for T-cell development, and their injury limits thymus function. We explain how TEC development creates multifunctional cortical and medullary microenvironments and describe regenerative pathways where TEC targeting creates therapeutic opportunities to restore T-cell immunity.

Thymus and T Cell Development Focus
In Special Collection: Autoimmunity 2024

This review highlights how novel cutting-edge technologies, including high-resolution imaging, single-cell omics, and organoid cultures, have improved our understanding of human thymus biology, in terms of developmental trajectories, cellular heterogeneity, and spatial organization.

Brief Definitive Reports

Infection with tick-borne encephalitis (TBE) virus (TBEV) is usually benign but may cause severe encephalitis in rare cases. Pre-existing autoantibodies neutralizing type I IFNs underlie ∼10% of these severe cases, strongly increasing the risk of severe disease relative to the absence of these autoantibodies.

Technical Advances and Resources

In Special Collection: Cytokines Collection 2024

Hahn et al., present data from a first-in-human HIV vaccine trial with a novel TLR-7/8-signaling adjuvant (3M-052AF/Alum). The vaccine appears safe and is the first vaccine reported to induce serum antibodies that neutralize non-lab-adapted HIV strains matched to the vaccine.

We developed a lymphoid organ-chip that models human recall responses to vaccination. This microfluidic-based system recapitulates antigen capture/expression, CD4+ T cell/B cell clustering, memory B cell amplification, plasmablast differentiation, and antibody secretion in response to perfused proteins or mRNA vaccines.

Trajectory analysis of CD4+ T cell differentiation during a type I inflammatory immune response identified two distinct differentiation paths for effector and precursor central memory T cells arising from heterogeneous naïve CD4+ T cells.

Articles

Iron-rich tumor-associated macrophages (iTAMs) are characterized by high intracellular iron, heme metabolism, and expression of the endothelin receptor type B. iTAMs promote angiogenesis and immunosuppression in tumors. Heme-mediated degradation of the transcriptional repressor BACH1 induces the iTAM transcriptional program in macrophages.

Miao et al. report that tumor cell–intrinsic mechanical force sensor, Piezo2, impedes stemness maintenance of CD8+ T cells by downregulating IL-15 production after radiotherapy, thereby leading to cancer radioresistance.

SETD1B (KMT2G) is a histone H3K4 trimethyl transferase and a mutational target in lymphoma. SETD1B inactivation disables critical cell death programs and causes Venetoclax resistance. Inhibition of the corresponding histone demethylase KDM5 restores cell death and Venetoclax sensitivity.

In Special Collection: Cytokines Collection 2024

The AMADEUS trial reveals key biomarkers in blood and tumor tissue that could predict patient response to immunotherapy, offering a potential breakthrough for treating various solid tumors. This discovery addresses the pressing need for personalized cancer treatment strategies.

This study shows NLRP3 inflammasome activation in circulating myeloid cells by human RAC2 gain-of-function variants that are linked to rare immune disorders. This work unravels a RAC2–PAK1–NLRP3 signaling axis as a potential drug target to treat patients.

The transit-amplifying (TA) cells at the intestinal crypt have the capability to proliferate, differentiate, and undergo regeneration upon injury. Angelis et al. show that ARID3A functions to fine tune the proliferation–differentiation dynamics at the TA cells and regulate injury-induced regeneration.

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