Issues

This work provides the first evidence that HSC directly sense Brucella abortus via the bacterial outer membrane protein Omp25 and the HSC surface receptor CD150, leading to functional commitment of HSC to myeloid lineage and very early initiation of immune response.

Mayrhofer et al. report that neurons in the mouse central nervous system receive nuclear and ribosomal material from Sox10-lineage cells. They identified nuclear interaction between satellite oligodendrocytes and neurons, suggesting a larger role of oligodendroglia in neuronal activity than previously thought.

GRB2 has numerous documented binding partners and is implicated in the regulation of several signaling responses in diverse cell types. Here, we show that the main function of GRB2 in thymocytes is to facilitate THEMIS-mediated inactivation of the tyrosine phosphatase SHP1.

Impaired lymphatic drainage of brain waste occurs in aging and disease, but the cause remains elusive. Here, Rustenhoven et al. describe how meningeal immune cell–derived IFNγ underlies this age-related deficit and demonstrate its therapeutic manipulation to improve waste clearance.

Overactivated ILC2s express TIGIT that induces activation-induced cell death via cell–cell contact with alveolar macrophages, which suppresses overwhelmed inflammation caused by chronic allergy.

Prior stimulation with bacterial and viral products followed by the loss of Tet2 remodels the transcriptional and epigenetic landscapes and cellular functions in HSCs via the Trif-Plk-Elf1 axis and drives the development of MDS.

Genetic deficiency of myeloid Src-family kinases protects mice from development of autoinflammatory diseases including gout and the systemic inflammation in motheaten viable mice. Src-family kinases are required for proinflammatory functions of neutrophils but not for their intrinsic migratory capacity. Dasatinib administration inhibits gouty arthritis.

Hui and colleagues show that CTLA4 acts in cis to deplete T cell–associated B7 ligands and that ipilimumab treatment inhibits this process to promote T cell autostimulation. This suggests a novel aspect of CTLA4 function with therapeutic implications.

This study uses a cell-free antigen processing system that mimics major histocompatibility complex Class II processing to reveal factors influencing epitope selection across the HIV-1 proteome. Novel epitopes are identified, and epitopes revealed from cell-free processing are primed in vivo.

In the oral mucosa, Stolley et al. characterize resident memory T cell (T_RM) distribution, ontogeny, role in protective immunity, and diverse functions, while describing strategies for locally augmenting or systemically depleting CD103⁺ T_RM.

This work provides a compendium of early transcriptional responses to “common-gamma-chain” cytokines across all major immunocyte lineages of the mouse.

The properties of human macrophages in non-diseased tissues are poorly understood. Here, Alaoui et al. identify three macrophage subsets in human tonsils, displaying distinct transcriptome, life cycle, and function. Short-lived macrophages are specialized for stimulating T follicular helper cells, due to cell-intrinsic features.

The fundamental importance of the role of human B cells in host defense against infectious diseases has been established by the discovery of inborn errors of immunity that disrupt B cell development, differentiation, or function. These findings have laid the groundwork for understanding mechanisms of disease and revealing pathways to improve humoral immunity and treat disease.

In this Review, we discuss the key features of type 2 inflammation in asthma, summarize the clinical trial evidence of monoclonal antibody asthma treatments, and explore future avenues for targeted asthma treatment.

In this issue of JEM, Xiaozheng Xu et al. report that the inhibitory protein CTLA4 internalizes in cis the B7 stimulatory molecules previously “gnawed” by T cells from APCs and in doing so prevents stimulatory T–T interactions.

Intercellular material transfer in the central nervous system (CNS) supports neuronal survival and activity. Mayrhofer et al. characterize extensive regionally coordinated transfer of oligodendroglial ribosomal and nuclear material toward neurons, linked to satellite oligodendrocyte–neuron pairs in the mouse CNS.

Stolley et al. discovered that the oral mucosa houses CD8⁺ CD103⁺ resident memory T cells, which are important for protecting against local viral infections in mice.