Fibroblastic reticular cells are the source of Notch ligands promoting the differentiation of short-lived effector CD8⁺ T cells. Induction of early Notch signals in CD8⁺ T cells enhances the opening of chromatin regions occupied by bZIP transcription factors.

This study demonstrates that impaired T cell receptor–induced CARD11-dependent JNK signaling results in upregulation of GATA3 and NFAT2, two key proteins in the development of T_H2 cells, identifying a novel molecular mechanism by which dominant interfering CARD11 variants spur the development of atopic disease.

Autoantibodies neutralizing IFN-Is exacerbate severe viral diseases such as COVID-19. Here, the authors identify IFN-I regions commonly targeted by these autoantibodies, characterize the pathogenic mechanism of autoantibody action, and develop a proof-of-concept inhibitory decoy strategy to alleviate IFN-I autoantibody effects.

PGD₂ released after NAIP-NLRC4 inflammasome activation in tuft cells signals onto ILC3s and mediates host defense mechanisms against Salmonella Typhimurium within the small intestine. Tuft cells therefore not only promote immune reactions against parasites, but also bacteria.

Jang et al. report that when the activating Kras mutation arises in hematopoietic stem cells, it causes the expansion and reprogramming of multipotent progenitors. These hypercompetitive progenitors lack self-renewal but rapidly spread the mutation throughout the blood system.

This work demonstrates that group 2 KLF family transcription factors are critical for specifying the identity of distinct tissue-resident macrophages. KLF2 directly controls expression of genes previously shown to be necessary in cavity macrophages, while KLF4 may play a similar role in alveolar macrophages.

Broomfield et al. demonstrate that early type I interferon blockade alters CXCR3 chemokine regulation and cell location to promote an antigen-dependent CD8⁺ T cell transition of precursor of exhausted T cells to stem cell–like memory CD8⁺ T cells for enhanced protection following viral infection and mRNA–lipid nanoparticle vaccination.