Computationally Designed Proteins Mimic Antibody Immune Evasion in Viral Evolution

Academic Background The continuous mutation of SARS-CoV-2 has posed ongoing challenges to the efficacy of vaccines and antibody therapies. Traditional evaluation methods can only test against existing variants and fail to predict future immune escape mutations. To address this, Noor Youssef and colleagues developed the EVE-Vax (Evolutionary Variant...

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...

Interleukin-34-Dependent Perivascular Macrophages Promote Vascular Function in the Brain

Academic Background Macrophages in the central nervous system (CNS) include microglia and border-associated macrophages (BAMs). BAMs are distributed in the meninges, choroid plexus, and perivascular spaces, with perivascular macrophages (PVMs) being closely associated with cerebrovascular function. However, the mechanisms underlying BAM maintenance...

Somatic Hypermutation Unlocks Antibody Specificities Beyond the Primary Repertoire

Academic Background One of the defining features of the adaptive immune system is its ability to generate highly diverse antigen receptors through V(D)J recombination, enabling recognition of a broad range of pathogenic threats. The traditional view holds that somatic hypermutation (SHM) in germinal centers (GCs) can only optimize pre-existing anti...

A Hierarchy of Intestinal Antigens Instructs the CD4+ T Cell Receptor Repertoire

I. Research Background The intestinal immune system must balance tolerance and defense against dietary antigens, microbiota-derived antigens, and self-antigens. Although CD4+ T cells are known to play a central role in gut immunity, how different antigen sources shape the composition of the T cell receptor (TCR) repertoire remains unclear. The trad...

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...