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...