Issues

Golnaz Vahedi is an associate professor of genetics at the Perelman School of Medicine, University of Pennsylvania. Golnaz runs a multidisciplinary lab that uses cutting-edge computational and experimental approaches to understand the molecular mechanisms through which genomic information in our immune cells is interpreted in normal development and during immune-mediated diseases.

In this issue of JEM, Foreman et al. report that, in tuberculosis granuloma, CD4 T effector cells require signals through CD30, potentially provided co-operatively by other T cells, to completely differentiate and protect against disease.

Kanta Subbarao and Brad Gilbertson discuss the concerns of pandemic potential of currently circulating highly pathogenic avian influenza H5N1 viruses.

PML nuclear bodies are stress-responsive domains involved in senescence, apoptosis, or metabolism. PML is required for response or even cure of some hematological malignancies. The authors review how PML participates in cancer cell clearance and highlight its druggable aspect.

ZBP1 is an innate immune sensor for double-stranded nucleic acids adopting the Z conformation. Z-RNA/DNA is generated during viral infections and in autoinflammation and cancer. By inducing regulated cell death and proinflammatory signaling, ZBP1 plays multifaceted roles in disease pathology.

Using antigen-induced arthritis (AIA) model, Zec et al. show that synovial lining macrophages undergo IRF5-dependent activation and produce CXCL1 as a result of antigen recognition. Consequently, neutrophils are preferentially recruited in the synovial lining niche at the onset of inflammation.

Foreman et al. find CD30 is preferentially expressed on granuloma T cells in Mtb-infected macaques. In mice, CD30 drives T cell differentiation and is required for host survival of Mtb infection, showing T cell immunity to Mtb requires CD30-dependent co-stimulation.

E3 ubiquitin ligase ZNRF1 is activated by c-Src kinase following TLR3 activation and, in turn, promotes TLR3 ubiquitination and trafficking to lysosomes for degradation. This leads to properly regulated interferon production and alveolar barrier repair to prevent secondary bacterial superinfection.

Understanding the unique features of immune functions of HLA-E to inform future clinical exploitation requires detailed knowledge of HLA-E transport. He et al. characterize the basic trafficking patterns of HLA-E within cells and how this trafficking is regulated.

Lockhart et al. demonstrate that exposure to food protein drives an antigen-specific CD4⁺ T cell response characterized at steady state by accumulation at the intestinal epithelium and tissue-specialized transcriptional imprinting. This process is disrupted upon either allergic sensitization or tolerance.

Neonatal life signals shape effective adult immunity. This study shows that type 3 γδ T cells and ILC3 require cIAP ubiquitin ligases from late neonatal life and thereafter to fully mature, survive, and establish normal barrier immunity.

A novel ILC2 subset was identified in the mouse intestine that constitutively expresses IL-4. Although the absence of the gut microbiota had marginal effects, feeding mice with a vitamin B1-deficient diet compromised the number of intestinal IL-4⁺ ILC2s.

The role of B cells in T1D remains poorly understood. We identified an activated B cell subset that is enriched in insulin reactivity and increased in the blood and pLN of T1D donors. This subset has capacity to secrete antibodies and potential to serve as APCs to T cells.

Li et al. reveal that the TRAF3–EWSR1 signaling axis serves as a critical checkpoint in the regulation of induced germinal center (GC) responses and immunoglobulin production. This signaling axis acts as a negative regulator of Bcl6 upregulation, which in turn negatively affects GC B cell generation and IgG production.

We analyze the ability of breast milk–derived immunoglobulin A (IgA) antibodies to bind bacteria commonly found within the preterm infant intestinal microbiota. We discover that each mother secretes into their breast milk a distinct set of IgA antibodies that are stably maintained over time.

Kang et al. identify a novel secretory subset of myeloid-biased multipotent progenitors, MPP3, which enforces myeloid lineage differentiation through lineage-priming and cytokine secretion and serves an essential regulatory function to amplify myeloid cell production in stress and disease conditions.

Obesity is associated with enhanced breast cancer mortality, yet the mechanisms underlying this relationship remain poorly understood. McDowell et al. provide insight into the role of obesity on myeloid-driven cancer metastasis by identifying how monocyte development is skewed to promote prometastatic neutrophil effector functions.

This study shows that intratumoral injection of engineered non-replicative recombinant modified vaccinia virus Ankara depletes and reprograms tumor-infiltrating regulatory T cells via OX40L–OX40 interaction and IFNAR signaling to enhance antitumor immunity.