Siniscalco et al. reveal that DOCK8 and STAT3 cooperate in CD4⁺ T cells to restrain Tfh13 differentiation and prevent food-specific IgE. The DOCK8-STAT3 axis functions cell-intrinsically within T cells to limit GATA3 expression and Tfh13 cell differentiation, while additional Treg impairment in DOCK8 deficiency uniquely enables Tfh13 induction in the gut.

Our study demonstrates CD205 is upregulated in prePCs. H3K27 demethylase Kdm6b, not Kdm6a, allows prePCs to become bona fide PCs by removing H3K27me3 marks at the Irf4 locus. Interestingly, prePCs favor glutamine metabolism, which provides α-ketoglutarate as a substrate for the demethylation reaction of Kdm6b.

Immune responses to pathogens lead to the generation of plasma cells containing the infection by secreting high-affinity antibodies. Here, we describe an in vivo CRISPR/Cas9 screening system for identifying novel regulators of B cell activation and plasma cell development in the context of the splenic microenvironment of immunized mice.

Single-cell and spatial transcriptomics of human TB lung tissues from individuals in South Africa revealed that MMP1⁺CXCL5⁺ fibroblasts and SPP1⁺ macrophages are linked to TB disease and TB lung granuloma, uncovering targetable cellular cross talk underlying TB immunopathology and potential avenues for host-directed therapies.

Březina et al. demonstrate that Claudin 1 enables thymic type 1 dendritic cells to localize within proximity to medullary thymic epithelial cells. This spatial arrangement supports maturation and tolerogenic function of type 1 dendritic cells, thus preventing disruptions in T-cell tolerance.

Lettera et al. show that human hematopoiesis across aging is characterized by stable stem cell numbers and reduced erythroid/lymphoid output. Aged HSPCs retain engraftment yet exhibit impaired differentiation, altered chromatin states, inflammatory signatures, DNA damage, and senescence under stress. Proliferative stress in cord blood HSPCs recapitulates these defects, establishing a model for age-associated hematopoietic decline.

Bittar et al. describe expanded clones of authentic CD4⁺ T cell carrying intact latent HIV-1 proviruses derived from people living with HIV. Their transcriptome mirrors their primary cells of origin. Notably, only a fraction of clonal cells express HIV. Latency-reactivating agents induce modest and variable activation, highlighting challenges in pharmacologic approaches to reservoir elimination.