Cholesterol increases macrophage-mediated inflammation, but how oxysterols control tumor-associated macrophages (TAMs) remains unclear. Xiao et al. show that TAMs exhibit elevated expression of CH25H, resulting in lysosome-accumulated 25HC that activates AMPKα to promote STAT6-dependent ARG1 production. CH25H-deficient macrophages switch “cold tumors”...

Signaling via Notch receptors intrinsically regulates tumor cells, promoting tumor progression. Mandula et al. examine the impact of Notch ligands on cancer cells on anti-tumor immunity in lung cancer and find that deletion of Jagged2 promotes expansion of immunostimulatory macrophages and anti-tumor T cell immunity. Mechanistically, in the absence...

Cis-regulatory elements and trans-acting factors coordinate to regulate T helper cell differentiation. Liu et al. characterize the histone modification and chromatin interaction dynamics in this process. The H3K4me1 landscape established by MLL4 in naive CD4+ T cells is critical for rewiring the chromatin interaction network orchestrated by GATA3 during...

Intraepithelial mast cells (IEMCs) were first observed 105 years ago, yet their functions remain enigmatic. Yang et al. reveal that IEMCs are required for epithelial gasdermin C activation and IEMC-epithelium crosstalk constitutes a critical step in type 2 immune responses.

Chronic viral infection disrupts the ability to form long-lived B cell-mediated protective immunity, but the mechanisms are unclear. Cooper et al. demonstrate a key role of type I interferon (IFN-I) in governing memory B cell identity and show that the chromatin landscape and phenotype of memory B cells are set during a critical early window of IFN-I...

Most bNAbs from chronically HCV-infected people use the VH1-69 gene segment and target the envelope glycoprotein E2 front layer. Ogega et al. isolate bNAbs from an elite neutralizer who spontaneously cleared HCV. These bNAbs use a variety of VH genes and target three E2 antigenic sites, including sites previously thought to be non-neutralizing. These...