There are no effective approaches to overcome the immunosuppressive activity of tumor-associated macrophages (TAMs). De Leo et al. report that monocyte-derived macrophages (MDMs), but not microglia (MGs), are major contributors to the immunosuppression associated with TAMs in glioblastoma and demonstrate that PERK-perturbed glucose metabolism drives...

The ubiquitin-binding endoribonuclease N4BP1 integrates signals from multiple innate immune receptors to regulate inflammatory cytokine responses. Gitlin et al. find that N4BP1 acts in concert with the noncanonical IκB kinases, TBK1 and IKKε, to suppress late-phase inflammatory gene transcription during Toll-like receptor responses, thereby limiting...

Mulè et al. provide a framework for integrating human population and single-cell variations to study vaccine responses with and without the adjuvant AS03. They uncover AS03-specific B cell survival and innate-sensing signatures 1 day after vaccination. Furthermore, some AS03-induced response cell states are already present at baseline in "naturally...

TLR7 is critical for recognizing RNA virus infection and initiating antiviral responses. Bérouti et al. demonstrate how RNase T2 and PLD exonucleases generate RNA fragments for TLR7 activation, thus providing insights into immune recognition of exogenous RNAs, with potential therapeutic implications.

Multilayered gene regulation orchestrates cell-type-specific cytokine expression. Liu et al. examine the impact of chromatin loop formation on the expression of IFN-γ and IL-22, which are cytokine loci closely located in the genome, and identify an inducible topologically associating domain required for proper IFN-γ production in Th1 cells. Deleting...

Regulatory T (Treg) cells in epidydimal visceral adipose tissue (eVAT) regulate metabolic homeostasis. Wang et al. identify a distinct compartment of eVAT-Treg cells that rein in the differentiation of adipocytes from stromal progenitors via the molecular mediator oncostatin M, thereby promoting insulin sensitivity and metabolic health.