IRF8 as durable architect of the microglial chromatin landscape.

被引量：- 发表：2024

IRF8 defines the epigenetic landscape in postnatal microglia, thereby directing their transcriptome programs.

被引量：1 发表：1970

The complexity of immune evasion mechanisms throughout the metastatic cascade.

被引量：1 发表：1970

Dual blockade of IL-10 and PD-1 leads to control of SIV viral rebound following analytical treatment interruption.

被引量：- 发表：1970

An IGHG1 variant exhibits polarized prevalence and confers enhanced IgG1 antibody responses against life-threatening organisms.

Evolutionary pressures sculpt population genetics, whereas immune adaptation fortifies humans against life-threatening organisms. How the evolution of selective genetic variation in adaptive immune receptors orchestrates the adaptation of human populations to contextual perturbations remains elusive. Here, we show that the G396R coding variant within the human immunoglobulin G1 (IgG1) heavy chain presents a concentrated prevalence in Southeast Asian populations. We uncovered a 190-kb genomic linkage disequilibrium block peaked in close proximity to this variant, suggestive of potential Darwinian selection. This variant confers heightened immune resilience against various pathogens and viper toxins in mice. Mechanistic studies involving severe acute respiratory syndrome coronavirus 2 infection and vaccinated individuals reveal that this variant enhances pathogen-specific IgG1+ memory B cell activation and antibody production. This G396R variant may have arisen on a Neanderthal haplotype background. These findings underscore the importance of an IGHG1 variant in reinforcing IgG1 antibody responses against life-threatening organisms, unraveling the intricate interplay between human evolution and immune adaptation.

被引量：1 发表：1970