Volume 26 Issue 10, October 2025

The effector fates of innate lymphoid cells (ILCs) are epigenetically imprinted early in ontogeny through the selective loss of DNA methylation at signature genes encoding fate-determining regulators — a process that is important for functional diversification of barrier immunity.

CD4⁺ T follicular helper (T_FH) cells that develop in response to a range of pathogens share aspects of a common gene signature. However, cytokine environments, rather than pathogen class, shape diversity in programming potential.

HIV drives host cells into dormancy within days of infection, actively laying the groundwork for latency and long-term persistence.

The pre-T cell receptor is essential for T cell development. It is also an emerging immunotherapy target.

The artificial intelligence (AI)-designed peptide SK56 blocks mature gasdermin D pores, delaying pyroptosis and inflammatory cytokine release. This reduces dendritic cell hyperactivation and prevents the spread of pyroptosis to nearby cells. SK56 also protects against mitochondrial damage and improves survival in septic mice, demonstrating its potential as a new post-pyroptosis, anti-inflammatory therapy.

Cholesterol-dependent cytolysins produced by diverse bacterial pathogens are internalized by host cells and translocate to the trans-Golgi network (TGN). They remodel the TGN into a platform for assembly of the NLRP3 inflammasome, a crucial innate immune signaling pathway in host defense and pro-inflammatory diseases.

We identified T cell receptors (TCRs) targeting antigenic peptides that contain a shared β-catenin mutation (CTNNB1^S37F) presented on common human leukocyte antigen alleles. TCR-engineered T cells eliminated patient-derived tumors and prevented relapse in vivo in mice, highlighting a strategy to exploit public neoantigens for TCR-based immunotherapy in solid cancers.

Our study defines and spatially maps skin fibroblasts in both health and disease. We categorize fibroblast subtypes based on their association with scarring risk across 23 skin diseases and perform cross-tissue comparisons to identify shared fibroblast states.

Here Iliev et al. review the interactions between the microbiota and the mucosal immune system from infancy to adulthood, highlighting the impact on health and disease.

Wang and colleagues show that an AI-assisted designed peptide obstructs GSDMD pores and inhibits IL-1β and IL-18 release and pyroptosis.

Chen and colleagues show that type A cholesterol-dependent cytolysins, a group of bacteria pore-forming toxins, translocate to the trans-Golgi network to remodel it into a platform for NLRP3 activation.

Wang and colleagues show that specific DNA methylation profiles mark the ILC progenitors (ILCP) that would differentiate into ILC1, ILC2 or ILC3 subsets.

The thymus is sensitive to acute insults including infection, as well as to injury from chemotherapy and myeloablative conditioning before hematopoietic cell transplantation. Here, Granadier et al. describe a role for IL-18 in limiting thymic regeneration by stimulating NK cells, which then target thymic epithelial cells.

The authors identify pre-TCR as a key biomarker and therapeutic target in T-ALL. Targeting it with an anti-pTα antibody–drug conjugate inhibits leukemia-initiating cells and tumor growth in mice, offering promise for relapsed/refractory T-ALL treatment.

TCR-T cells are T cells engineered to express a specific T cell receptor. Here the authors present a TCR-T cell that targets CTNNB1-S37F, corresponding to a shared cancer driver mutation. This immunotherapy killed solid tumors when applied to a patient-derived xenograft model in mice.

Cui and colleagues identify the chromatin organizer protein SATB1 as a critical regulator of quiescence in stem-like progenitor CD8⁺ T cells that arise during chronic viral infection and cancer.

Here the authors show a function for lymph nodes in the maintenance of effector T cell differentiation and function during chronic infection and checkpoint blockade, identifying a spatial component in the regulation of exhausted T cell fitness.

Sawada et al. show simultaneous activation of the STING and lymphotoxin beta receptor signaling induces B cell-activating germinal center responses within tumor environment and enhances antitumor responses.

Erlich et al. show that soluble LTα and membrane-bound LTα1β2 lymphotoxins expressed by B cells play distinct roles to attenuate the pathology observed in ileitis.

Here the authors spatially map human pediatric low-grade gliomas using imaging mass cytometry, focusing on immunosuppressive myeloid cell populations and their functionality in tumor–immune interactions and tumor progression.

Steele et al. use single-cell RNA sequencing and spatial transcriptomics to provide an atlas of adult human skin fibroblasts in healthy and diseased human skin.

Dalit, Tan and colleagues provide a multiomic profile of T follicular helper (T_FH) cells responses to diverse pathogens, revealing a blueprint for transcriptional flexibility and new tools to interrogate T_FH heterogeneity in mice and humans.