Issues

The gut microbiome limits neuroinflammation and neurocognitive decline in acute graft-versus-host disease by modulating microglial activation via a mechanism mediated by the microbial metabolite TMAVA.

Geng et al. show that LEC S1P/S1PR1 signaling plays a role in mesenteric TLS formation in the absence of subclinical inflammation and, importantly, is a key regulator of lymphatic valve development.

In this viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher.

While CD8 T cells are important for anti-tumor immunity, CD4 T cells are increasingly recognized as key determinants of tumor rejection. This review describes how tumor-reactive CD4 T cells are functionally impaired, including similarities/differences with CD8 T cells, and how immunotherapies can help overcome this.

This review highlights how memory T cells fight infections and cancer by retaining epigenetic “memories” that enable the rapid reactivation of inflammatory genes. The authors also discuss how such epigenetic mechanisms may fuel T cell dysfunction in disease, including T cell exhaustion in cancer.

Cancer and cardiovascular disease are the leading causes of death worldwide. Cancer patients display an abnormally elevated burden of cardiovascular disease. Here, we summarize the links between cancer and cardiovascular disease, highlighting the neutrophils’ dynamic interaction with both diseases.

Glial cells and lipoproteins coordinate lipid and immune signaling to regulate CNS inflammation. This review explores the relationship between lipid metabolism and inflammation and how disruptions in this interplay and contribute to neurological disorders.

Current mRNA vaccines have either limited efficacy or severe toxicity. This study highlights that next-generation mRNA vaccines encoding membrane-tethered cytokine adjuvants can generate potent pre-effector cells, offering effective tumor control with reduced toxicity.

Monoallelic mutations, p.A116V and p.R126P, in MMD2 disturb fMLP-induced activation of Ras/ERK signaling and underlie the impairment of neutrophil chemotaxis, which leads to the development of the autosomal dominant form of aggressive periodontitis.

Plasmodium falciparum circumsporozoite protein harbors conserved human T cell epitopes that may serve as targets for broad strain-transcending immunity. The findings offer guidance for the design of improved malaria vaccines.

Cachexia is a devastating cancer comorbidity that impacts numerous cancer outcomes, including therapeutic efficacy, quality of life, and overall survival. This work describes a novel metabolic pathway/target with clinical implications for the treatment of cachectic pancreatic cancer patients.

In this study, we report that microbiota depletion exacerbates acute graft-versus-host disease in the central nervous system, driven by microglial activation and T cell infiltration. Administration of the bacteria-derived metabolite N,N,N-trimethyl-5-aminovaleric acid could rescue both microglial activation and associated neurocognitive deficits.

TLOs are LN-like structures that are observed in certain inflammatory diseases. Geng et al. demonstrate that S1PR1 activity in the lymphatic vasculature is necessary to prevent TLO formation in the terminal ileum.

In this study, Gawish et al. show that RNA editing of the actin cross-linker FLNA is similarly regulated in mice and humans and that the targeted induction of edited FLNAR in myeloid cells governs resistance to DSS-induced colitis, revealing its potential in IBD therapy.

Type I IFN signaling contributes to arthritis pathogenesis in obesity through activation and expansion of CD8 T cells in visceral adipose tissue and synovium. Deletion of IFNAR1 in T cells reduces arthritis severity in obese mice.

During obesity, the bone marrow is dysregulated to overproduce myeloid cells that drive systemic inflammation. Neutrophil migration is a key mediator of this process, and targeting neutrophil movement during obesity or weight loss improves inflammatory and metabolic outcomes.

Lane et al. discover that the lymphatic vasculature is functionally and transcriptionally distinct along the gut. Duodenal lymphatic vessels appear optimized for dietary lipid uptake. Duodenal helminths compromise this property, providing an alternative explanation for worm-induced resistance to weight gain.

This study describes a Mycn-nGEMM for neuroblastoma. Murine and human neuroblastomas showed profound immunosuppression mediated by PD-L1–expressing, TAMs. Anti–PD-L1 immunotherapy depleted TAMs and inhibited tumor growth, demonstrating the potential for myeloid-targeted immunotherapies to overcome the immuno-inhibitory barriers.

This paper uncovers an unexplored metabolic symbiosis between tumor cells, CAFs, and TAMs. The authors show how tumor-derived lipids can induce an IL-6–dependent increased glutamine synthesis pathway in CAFs, supporting CAFs ability to promote pro-tumorigenic TAMs.