Horton et al. report that force generated by blood flow within the developing embryo dictates a bioenergetic switch necessary for hematopoietic stem cell emergence. Shear stress triggers protein translation and transcriptional upregulation of mitochondrial genes via mTORC1 to endow stem cells with blood reconstitution capacity.

Hu et al. identify transcriptional repressor REV-ERB as a critical regulator of colonic RORγt+ Treg differentiation and function through the Bhlhe40-c-Maf axis, highlighting its potential as a target for improving Treg cell function in inflammatory bowel diseases.

We identified peptide sequence principles that drive dendritic cell maturation and broaden tumor-reactive T cell clones, even with non-tumor sequences. These peptides must be expressed intracellularly in vivo as single chain containing MHC class I– and II–restricted non-self immunogenic epitopes.

Fulminant viral hepatitis (FVH) is a devastating condition caused by hepatotropic viruses. In 149 international FVH patients, auto-Abs neutralizing type I interferons are found in 37.5% of HSV-triggered cases and are absent in hepatitis A and B virus–triggered cases, increasing the risk of HSV-FVH by >1,800-fold.

Zhang et al. report a fatal case of avian influenza H5N1 infection caused by autoantibodies neutralizing type I IFNs. These rogue autoantibodies are common, especially in elderly people. They are found to underlie a growing range of severe infections of emerging and circulating viruses, including seasonal influenza viruses and SARS-CoV-2.

Rhodehouse et al. characterize a nonhuman primate model of natural control of SIV infection in which the immune system blocks new infection events with an efficiency approaching that of antiretroviral therapy.

The functional dynamics of the Runt-related transcription (RUNX) factors in initiating T-lineage programs remain unclear. Kama et al. show that Notch-mediated reorganization of RUNX complexes and redeployment of RUNX-binding genomic regions are crucial for triggering the T-lineage program.