Microglia Transcriptional States and Their Functional Significance: Context Drives Diversity

Academic Background Microglia are the only resident macrophages in the central nervous system (CNS) and play critical roles in development, homeostasis, and disease. Traditionally, microglia were viewed as homogeneous “resting” or “activated” states, but the advent of single-cell sequencing technologies has revealed their remarkable transcriptional...

Inflammasome Signaling in Astrocytes Modulates Hippocampal Plasticity

Academic Background In recent years, the role of immune signaling pathways in nervous system homeostasis has garnered increasing attention. Traditionally, the inflammasome, a core complex of innate immunity, was thought to activate only during infection or tissue damage, participating in pathological processes through caspase-1-mediated pyroptosis ...

IL-10 Sensing by Lung Interstitial Macrophages Prevents Bacterial Dysbiosis-Driven Pulmonary Inflammation and Maintains Immune Homeostasis

1. Research Background The pathogenesis of chronic lung inflammation and pulmonary fibrosis remains unclear, particularly regarding the interaction between pulmonary commensal microbiota and the immune system. While interleukin-10 (IL-10), a key anti-inflammatory cytokine, has been extensively studied in gut homeostasis, its role in pulmonary immun...

Alcaligenes faecalis Induces Intestinal T Helper 17 Cells by Promoting E3 Ubiquitin Ligase TRIM21-Mediated FBXW7 Degradation

1. Research Background Intestinal Th17 cells play a central role in maintaining mucosal immune homeostasis and defending against pathogen infections. Previous studies identified segmented filamentous bacteria (SFB) as key microbes inducing intestinal Th17 cells, but controversies exist regarding SFB colonization in adult intestines: 1. Clinical Par...

Phosphoantigen-Induced Inside-Out Stabilization of Butyrophilin Receptor Complexes Drives Dimerization-Dependent γδ TCR Activation

Academic Background γδ T cells are a unique subset of the immune system, characterized by T cell receptors (TCRs) composed of γ and δ chains that recognize non-peptide antigens, such as phosphoantigens (PAgs) produced by microbial or tumor cells. Among them, Vγ9Vδ2 T cells are the most abundant γδ T cell subset in human circulation and play a criti...

Direct Microglia Replacement Reveals Pathologic and Therapeutic Contributions of Brain Macrophages to a Monogenic Neurological Disease

Academic Background Krabbe disease (also known as globoid cell leukodystrophy, GLD) is a fatal pediatric neurodegenerative disorder caused by mutations in the galactosylceramidase (GALC) gene. A hallmark pathological feature of this disease is the presence of lipid-laden globoid cells (GCs) in the central nervous system (CNS). Currently, hematopoie...

Monocytes Can Efficiently Replace All Brain Macrophages and Fetal Liver Monocytes Can Generate Bona Fide Sall1+ Microglia

Academic Background The homeostasis of the central nervous system (CNS) relies on two key types of macrophages: microglia and border-associated macrophages (BAMs). Traditionally, microglia are believed to originate from the embryonic yolk sac and possess lifelong self-renewal capabilities, while bone marrow (BM)-derived monocytes in adults cannot r...

Vaccination of Nonhuman Primates Elicits a Broadly Neutralizing Antibody Lineage Targeting a Quaternary Epitope on the HIV-1 Env Trimer

1. Research Background The envelope glycoprotein (Env) of human immunodeficiency virus type 1 (HIV-1) is the primary target of neutralizing antibodies, but its high variability poses challenges for vaccine development. Broadly neutralizing antibodies (bnAbs) are rare in natural infections and typically require years to emerge. Although Env trimer m...

DDX24 Spatiotemporally Orchestrates VEGF and Wnt Signaling During Developmental Angiogenesis

Research Background Vascular system development is a highly precise regulatory process involving two key stages: vasculogenesis and angiogenesis. Although the VEGF (vascular endothelial growth factor) and Wnt signaling pathways have been confirmed to regulate vascular development in the peripheral and central nervous systems (CNS), respectively, th...

NF-κB-Mediated Developmental Delay Extends Lifespan in Drosophila

1. Research Background Aging has long been viewed as a gradual decline in physiological function with age. However, mounting evidence indicates that developmental programs profoundly influence aging outcomes. For instance, developmental time (the time required for an organism to reach maturity) shows a significant positive correlation with adult li...