Wang et al. analyze memory B cell and antibody responses in SARS-CoV-2 mRNA vaccines to breakthrough infections with Delta or Omicron BA.1 variants. Breakthrough infection after two or three doses of mRNA vaccination was comparable to three doses of vaccination in eliciting broad and potent memory B cells. The findings provide insights on broad and strain-specific memory responses after mRNA vaccination with Wuhan-Hu-1.

Nadkarni et al. show that human endothelial cells (EC) engage both NLRP1 and CARD8 inflammasomes. CARD8 is activated by Coxsackie B3 protease-mediated N-terminal cleavage. Knocking out CARD8 attenuates CVB3 propagation and dampens inflammation in a cellular model of viral myocarditis.

Sleep interruption restructures the epigenome of hematopoietic stem and progenitor cells (HSPCs) and increases their proliferation, priming them for exaggerated inflammatory bursts and reducing hematopoietic clonal diversity through accelerated genetic drift. In humans, sleep restriction alters the HSPC epigenome and activates hematopoiesis.

Advanced age is the most critical risk factor for severe COVID-19. Using a newly established mouse model, Beer et al. demonstrate that the age-dependent exacerbation of disease is driven by a diminished innate and adaptive immune response due to impaired type I and type II interferon responses.

This study demonstrates that GABA regulates intestinal stem cell apoptosis through its A receptor in chemoradiotherapy-induced intestinal injury. FDA-approved GABA_AR antagonist flumazenil may be a promising drug for reducing the gastrointestinal side effects brought by chemoradiotherapy.

c-MAF, highly expressed in villus small intestinal enterocytes, coordinates transcriptional programs for nutrient absorption. Enterocyte-specific c-MAF inactivation impairs dietary lipid handling but also leads to tuft cell expansion and adaptive gut lengthening, revealing crosstalk between enterocytes and tuft cells during intestinal adaptation.

This study identifies c-Maf as an enterocyte-specific transcription factor within the small intestinal epithelium. c-Maf governs the spatial and functional specialization of enterocytes, especially gene programs controlling intestinal nutrient absorption. Thus, epithelial c-Maf deletion results in impaired enterocyte maturation, nutrient uptake, and alterations of the immune system and microbiota.