Issues

In this issue of JEM, Wouters et al. challenge established genetic principles believed to govern DADA2, an inborn error of immunity.

This year at JEM, we are highlighting women in science by sharing their stories and amplifying their voices. 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.

KLA driven by somatic NRAS mutations in lymphatic endothelium, lacks animal models for study. A novel zebrafish model mimicking KLA features was developed, enabling high-throughput drug screening. Cabozantinib and GSK690693 show therapeutic promise, normalizing abnormal cell behavior and advancing treatment strategies for KLA.

This study analyzes the intrarenal myeloid compartment in four lupus nephritis mouse models and 155 humans using single-cell profiling, spatial transcriptomics, and functional studies. It identifies shared myeloid subsets linked to disease and tissue damage, supporting mouse models' relevance for human lupus nephritis interventions.

ILC2s can enter the brain parenchyma from the blood circulation early after ischemic stroke in a CXCR1-dependent manner. Once in the brain, ILC2s improve long-term recovery of sensory-motor functions by promoting initiation of angiogenesis, namely angiogenic sprouting.

Multiple omics analyses identified RUNX2 and BHLHE40 as key factors driving T_RM characteristic of Crohn’s disease. The overexpression of these transcription factors induced Crohn’s disease–specific T_RM, and blocking these transcription factors mitigated the cytotoxic T_RM phenotype in human disease samples.

The ANKRD55 locus has been associated with multiple autoimmune diseases. Using murine models of inflammation, Xu et al. demonstrate an important role of the ANKRD55 protein in T_H17 biology, where its deletion impairs T cell proliferation and effector cytokine production through metabolic dysregulation.

In this study, we develop a strategy for combining oncolytic virus and CAR-T therapy via specifically loading VSV onto the surface of CAR-T cells. This strategy can directly pre-activate CAR-T cells via cross-connection between viral particles and CAR moieties and induce immunological synapse formation.

NLRP3 is a target for anti-inflammatory therapies and can be inhibited by the tool compound MCC950. We describe the characterization of new small-molecule inhibitors of NLRP3, BAL-0028 and BAL-0598, that have a distinct mechanism of action and binding site.

Cheng et al. reveal that the PAC channel negatively regulates phagosome maturation in macrophages. PAC Channel deletion enhances bacterial clearance and immune responses, including STING-IFN and inflammasome activation, thus improving survival in bacterial infections.

Ocular commensal C. mast induces IL-17 responses from Vγ6 T cells, helping to maintain mucosal barrier function of the conjunctiva. Mechanistically, Vγ6 T cell–intrinsic TLR2 stimulation increases Il17a transcription and promotes fatty acid metabolism, favoring IL-17A responses.

Di Luccia et al. demonstrate that gut regulatory T cells are crucial to maintain the disease-tolerant state of asymptomatic carriers during Salmonella chronic infection. These findings provide novel insights into mucosal responses to persistent pathogens.

This study shows that next to biallelic deleterious mutations in ADA2, monoallelic dominant negative missense variants in ADA2 can also underlie ADA2 deficiency.

Whole-transcriptome sequencing, CRISPR dropout screens, and chemical screens identify AURKB dependency in advanced GISTs. AURKB inhibitors demonstrate potent efficacy in various preclinical GIST models at safe doses, overcoming TKI resistance. These studies provide non-receptor tyrosine kinase therapeutic strategies for clinical translation.