Epithelial tuft cells serve as intestinal immune sentinels, but why they secrete acetylcholine remains unknown. Billipp et al. show that tuft cell chemosensing leads to acetylcholine release, which induces secretion of chloride and subsequently water f…
Intestinal tuft cells are known as sentinels capable of initiating type 2 immune responses upon parasite infections. Ndjim et al. now report a direct effector function for intestinal tuft cells during such immune responses by increasing their acetylcho…
RIPK1 regulates cell death via kinase-dependent and kinase-independent mechanisms. Utilizing mice expressing RIPK1 with a point mutation disrupting its death domain, Imai et al. show that RIPK1 death domain interactions are critical to suppress ZBP1- a…
The inflammatory activity of IL-1 family cytokines is unleashed by caspase cleavage, but the underlying molecular mechanisms are unclear. Here, using cryo-EM and NMR techniques, Dong et al. reveal the conformational steps in the pathway for recognition…
Adaptive immunity to commensal microbes promotes tissue homeostasis, immunity, and repair, but approaches to identify commensal-specific B cell responses are lacking. Verma et al. utilize phage display screening and subsequent generation of B cell tetr…
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…
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 suppre…
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….
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 ind…
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 exogeno…
