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Individuals with SYK gain-of-function variants develop immunodeficiency and systemic inflammation, which are recapitulated in a knock-in mouse model. Treatment of these mice with bone marrow transplantation or with a SYK inhibitor ameliorates disease symptoms, highlighting potential therapeutic strategies for patients with SYK mutations.

Genetic variants in the SBNO2 locus are associated with Crohns’s disease. Here the authors show that those variants cause a cell type and isoform specific effect were transcription of SBNO2 isoform 2 impacts on antimicrobial activity in macrophages providing a plausible gene-mechanism-phenotype model.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

In this Resource, Buckley and colleagues profile patients with Crohn’s disease and ulcerative colitis before and after adalimumab therapy. Specific pretreatment differences in the epithelial and myeloid compartments were associated with remission outcomes in both diseases. The authors also describe the cellular circuitry in nonremission patients following treatment.

Diagnostic blood-based biomarkers of pediatric IBD are limited. Here, the authors demonstrate a diagnostic lipidomic signature, comprising only of two molecular lipids. Translation of this signature into a scalable test has the potential to support clinical decision making.

FitzPatrick et al. use single-cell RNA and spatial transcriptomics to dissect the immune microenvironments within the small bowel mucosa in celiac disease.

Adult forms of inflammatory bowel disease (IBD) are of a polygenic nature, but paediatric and very early onset (VEO) IBD also occur as monogenic forms. Here, using whole exome sequencing, the authors explore both the monogenic and polygenic contribution to VEO-IBD and characterize a rare somatic mosaic VEO-IBD patient.

Interactions between the host immune response and the commensal microbiota play essential roles in health and disease. Here the authors identify a population of MHC class II, innate like, commensal reactive cells in the gut of mice and humans.

Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

The cytokine interleukin (IL)-23 has inflammatory effects on innate immune cells and can drive colitis, but the cellular and molecular pathways involved are poorly characterized. Here it is shown that bacterial-driven innate colitis involves a previously unknown population of IL-23-responsive innate leukocytes that produce IL-17 and interferon-γ. These cells may represent a target in inflammatory bowel disease.

A deep-learning algorithm was developed to identify skin lesions caused by the mpox virus and was then implemented in a web-based app designed for patient use.

An oncometabolite produced by tumor cells acts as a paracrine immunosuppressant dampening antitumor T cell responses in glioma.

Transcriptomic and histological profiling of gut biopsies from multiple independent cohorts of patients with inflammatory bowel disease identifies distinct histopathological, molecular and cellular features associated with treatment response, providing insights for patient stratification and precision therapy.

Photosystem II is the biosynthetic machinery that allows the conversion of water to oxygen using light. Here, the authors combine X-ray emission and diffraction data to probe the structural changes that take place during photosystem II catalysis.

In this Expert Recommendation, Uhlig and colleagues review the therapeutic landscape for monogenic inflammatory bowel disease and propose recommendations for standardized reporting of clinical outcomes.

Photoinduced non-adiabatic intramolecular processes have important applications but their mechanisms are challenging to explore. Here the authors detect and assign vibrational wavepacket dynamics in a Fe carbene complex by ultrafast X-ray emission spectroscopy and X-ray scattering, resolving nuclear and electronic motion.

Gilean McVean and colleagues report the results of a large-scale clinical genome sequencing project spanning a broad spectrum of disorders. They identify factors influencing successful genetic diagnosis and highlight the challenges of interpreting findings for genetically heterogeneous disorders.

Mental and cardiovascular health interact in complex ways. Here, the authors demonstrate an association of blood pressure with depressive symptoms, well-being, and emotion-related brain activity that may be relevant to the development of hypertension.

BACH2 is required for lymphocyte differentiation. Afzali et al. describe mutations that cause BACH2 disruption, immunodeficiency and autoinflammatory disease via haploinsufficiency, a mechanism shared by other super-enhancer-regulated genes.

Photoinduced electron transfer in solvated molecular assemblies occurs on the ultrafast timescale before full electronic and geometric relaxation take place. Here Canton et al.monitor this out-of-equilibrium process in a donor–acceptor bimetallic assembly using an X-ray free-electron laser.

Roquin-1 is a posttranscriptional regulator that controls the expression of many immune-related genes such as ICOS and TNFA. Here, the authors report a homozygous R688* loss of function mutation in Roquin-1 in a patient with syndromic uncontrolled hyperinflammation associated with immune cell activation and hypercytokinemia.

The proximal small intestine is key for nutrition, metabolism and immune responses, and can be affected by a wide range of disorders. This Review describes the cellular and molecular bases of diseases of the proximal small intestine (including rare monogenic disorders), proposing a mechanism-based taxonomy.

While hundreds of loci are linked with inflammatory bowel diseases (IBDs), the functional consequences of the associated variants remain unclear. Here, the authors screened in ulcerative colitis (UC) patients’ genomes for protein-truncating variants near IBD loci, and identify a protein truncating variant in RNF186to be protective against UC.

Short-chain fatty acids (SCFAs) are microbial metabolites that regulate mucosal barrier integrity and immune cell functions. This Review summarizes latest insights into how SCFA levels might determine inflammatory and allergic disease outcomes by controlling the crosstalk between diet, the microbiome and immunity.

Green rust, a common mineral in Precambrian oceans, forms as a by-product of mackinawite partial oxidation by uranium, along with uraninite and polysulphide. This process is accompanied by a large uranium isotope fractionation, according to isotopic uranium concentrations obtained from experimental data.

Nectin-4 is identified as a receptor for measles virus on epithelial cells, and measles virus might use nectin-4 for emergence in the airways.

Biallelic loss-of-function mutations in TGFB1 are reported in three individuals with severe infantile inflammatory bowel disease and neurodevelopmental delay. These findings highlight a critical role for TGF-β1 in human intestinal homeostasis and central nervous system development.