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.

Li et al. find that in Paneth cells, ERAdP senses c-di-AMP derived from intestinal microbiota, activating DCV biogenesis and AMP secretion to enhance intestinal defense. The ERAdP–NLRP6–ANXA2 axis is impaired in IBD patients, suggesting this axis might be a potential therapeutic target for infection and inflammation.

Farré Díaz et al. describe a broadly applicable system for sequential targeted mutagenesis using two recombinases sequentially activated from a single locus. As a proof-of-concept experiment, the time-controlled re-expression of FOXO1 rescued the defects associated with FOXO1-deficient germinal center B cells, including class switch recombination, providing new insights into FOXO1 biology via a dual-recombinase tool.

Tet2^ΔMye exacerbates liver fibrosis through stabilizing Ccl2/Ccl8 mRNAs in pMDMs, creating a chemokine-driven inflammatory loop. Targeting this axis with Bindarit and IL-6 blockade synergistically reduces fibrosis associated with Tet2^ΔMye-related myeloid hematopoiesis.

Xu et al. demonstrate that FIP200, a sensor involved in autophagy regulation, governs the differentiation of plasma B cells. B cells without FIP200 are dysfunctional in mitophagy and metabolism. Adding heme can rescue this phenotype and allow plasma cell differentiation.

Antibiotic treatment in early life can deplete riboflavin-synthesizing commensals and impair mucosal-associated invariant T (MAIT) cell development, rendering adult animals more susceptible to bacterial pneumonia. Transfer of MAIT cells or administration of a riboflavin-synthesizing probiotic is sufficient to restore respiratory immunity.