Issues

This review summarizes evidence that both the mycobacterial-specific and off-target nonspecific effects of BCG immunization require the interplay of innate and adaptive responses and proposes that elucidating this interaction should be a major approach in developing more effective TB vaccines.

HAQ STING dominantly protects from clinical penetrance of COPA syndrome, revealing unexpected functional differences between common STING alleles. This represents the first report of a common allele providing complete clinical protection from a severe monogenic disorder.

Sex hormones and chromosomes work in tandem to impact immune responses, with estrogen influencing class-switched memory B cell frequency exclusively in individuals with an XX chromosomal background.

This work provides, as a resource, a compendium of early transcriptional responses to major inflammatory cytokines across all major immunocyte lineages of the mouse, bringing forth unappreciated relationships between these cytokines, and with other cytokine families.

Antibody depletion of select lymphocytes in rhesus macaques demonstrated key roles for CD4⁺ T cells and CD8α⁺ lymphocytes in conferring sterilizing immunity against tuberculosis following i.v. BCG vaccination. This study established mechanisms of protection that can inform future vaccine strategies.

This research shows that Th1 cells convert into T-bet⁺ pTreg cells in response to TGF-β signaling in the TME. Tan et al. demonstrate that T-bet is essential for the function of intratumoral pTreg cells, which exert suppressive activity via CD39.

This paper utilizes several genetic models to distinguish roles of cDC1 and cDC2 in presentation of different forms of antigens to CD4⁺ and CD8⁺ T cells in vivo. The results demonstrate a common WDFY4-dependent cross-presentation pathway shared by cDC subsets.

This study uncovers MLL3 mutations as early events driving UASCC development, highlighting their role in tumor evolution and immune modulation. It also identifies the MLL3/GRHL2-IRF1 axis as a promising therapeutic target for treating UASCC.

Wang et al. show that ZMIZ1 and MYB convergently activate an MYCN-centric transcriptional network in early T-cell precursor (ETP) cells that advances our understanding of the impact of stem cell gene expression in unifying the high-risk behavior of ETP leukemia.

Hepatic fibroblasts comprise groups of stromal cells in the liver that are phenotypically distinct from hepatic stellate cells. However, their physiology is poorly understood. This work used genetic fate mapping to unravel the functions of hepatic fibroblasts in liver homeostasis, fibrosis, and tumorigenesis.

Microglia contain Aβ plaques in Alzheimer’s disease (AD). In an AD mouse model, microglial Atg7 deletion impaired plaque coverage, increasing Aβ diffusion and neurotoxicity. This was linked to reduced unfolded protein response, increased oxidative stress, and ferroptosis of microglia.