Volume 24 Issue 7, July 2023

Presentation of signal peptides by HLA-E to natural killer cells prevents cell lysis via interactions with the inhibitory CD94–NKG2A receptor. A study now reveals an unexpected level of sophistication and heterogeneity in this receptor–ligand interaction.

Single-cell RNA sequencing distinguishes subsets of fibroblastic reticular cells and predicts pathways that support immune function via crosstalk with lymphocytes.

COVID-19 vaccines have been successful, but their duration and level of protection could be improved to cover all SARS-CoV-2 variants. A self-assembling enveloped virus-like particle vaccine combining features of mRNA and protein vaccines might provide a way forward.

The magnitude and quality of the germinal center response after vaccination decline with age. We found that T follicular helper (T_FH) cells are enriched in the dark zone of germinal centers in aged mice, which impairs the expansion of the follicular dendritic cell network upon immunization and reduces antibody responses.

We identified an abundant macrophage population with a distinct transcriptomic signature in the murine mammary gland and milk during lactation. These macrophages are monocyte-derived, depend on colony-stimulating factor (CSF-1) and reside adjacent to alveoli. Human milk also contains macrophages comprising three subsets with a partial resemblance to the murine counterparts.

Extravasation of blood into the brain and activation of innate immune cells are hallmarks and therapeutic targets in neurological diseases. We show that specific blood proteins induce distinct receptor-mediated gene programs in microglia and that the blood coagulation protein fibrin has a causal role in pathogenic innate immunity in models of neurological diseases.

Devant and Kagan review the biochemical and cell biological mechanisms that control gasdermin D pore-forming activity and its diverse downstream immunological effects.

Buggert and colleagues provide a broad picture in this review of circulating and tissue-resident memory CD8⁺ T cells, which are ultimately responsible for effective immune surveillance.

Human leukocyte antigen (HLA)-E binds epitopes derived from HLA-A, HLA-B, HLA-C and HLA-G signal peptides (SPs) and serves as a ligand for CD94/NKG2A and CD94/NKG2C receptors. Carrington and colleagues provide comprehensive analysis of classical HLA class I SP variants and show that these can determine CD94/NKG2–HLA-E engagement.

Greter and colleagues identify a population of CD11c⁺F4/80⁺CD64⁺MHCII⁺CX3CR1⁺ macrophages in the mouse mammary gland that is induced by lactation and resembles several subsets of macrophages detected in human milk.

Choi et al. show that infiltrating CCR2⁺ monocytes, by provision of IL-6, instruct tissue-resident microglia to become ‘repair-associated microglia’ following intracerebral hemorrhage, promoting cerebrovascular repair and neurological recovery.

Linterman and colleagues examine germinal center formation in older individuals. They find that aged T_FH cells have dysregulated CXCR4 expression, which causes spatial mislocalization of these cells in germinal centers, impairing their ability to provide help to B cells and to promote antibody production.

De Martin, Ludewig and colleagues define the topology and molecular identity of human tonsillar stromal cells and show that PI16-expressing fibroblastic reticular cells shape subepithelial niches for efficient T cell activation and differentiation.

Pikor et al. show that a set of conserved, bidirectional cues exchanged between fibroblastic reticular cells and immune cells sustain B cell niches, which control humoral immune responses across mouse and human lymphoid organs.

Kaplonek et al. provide a prospective look at ChAdOx1 nCoV-19-vaccinated individuals who go on to experience breakthrough COVID infections. They report an antibody Fc profile characterized by higher FcgR2b and reduced Fcgr3b for individuals who are more susceptible to breakthrough infections.

Akassoglou and colleagues provide a single-cell RNA sequencing and phosphoprotein analysis of the responses of central nervous system microglia and macrophages to blood proteins including activated complement and fibrin. Their findings point to potential therapeutic targeting of microglia activation by immune and vascular signals.

Glass and colleagues show that the transcription factor SALL1-associated super-enhancer is exclusively activated in microglia, in part through SMAD4-mediated signaling, and that SALL1 subsequently enforces microglia-specific functions of SMAD4.

Smith et al. present a resource detailing drivers of transcriptional heterogeneity of synovial fibroblasts cell states in the inflamed joints of human patients with rheumatoid arthritis.