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Post-translational modification of chemokines such as CXCL10 can regulate their activity. Albert and colleagues demonstrate that the endogenous peptidase DPP4 cleaves CXCL10 and thereby interferes with T cell recruitment to tumors.

Dietary fibre is metabolized into short-chain fatty acids by gut bacteria. Here the authors show that these metabolites activate the NLRP3 inflammasome in gut epithelial cells and protect mice from injury-induced colitis, suggesting a mechanism for the benefits of a high-fibre diet.

This preclinical study demonstrates the potential of a drug repurposing strategy using the coadministration of tamsulosin, metoprolol, and bromocriptine to provide a mutation-agnostic therapy for inherited retinal degeneration.

Here the authors show that genkwanin glycosides from Phaleria nisidai leaf extract improve glucose homeostasis by enhancing glucose uptake into adipose tissue, with effects comparable to metformin in a study with male mice with obesity and insulin resistance.

Simpson and colleagues systematically interrogate the influence of dietary carbohydrate type and quality on the obesogenic impact of protein-diluted diets in mice.

Here, the authors show that IRX3 is a transcriptional master regulator of multiple histone- and chromatin-remodeling enzymes and the SUMOylation pathway in adipocyte precursor cells. IRX3 ablation results in a SUMOylation-dependent switch from adipogenic to osteogenic identity.

Current preclinical models to investigate human HR + breast cancer progression and response to immunotherapy in vivo are limited. Here, the authors demonstrate that mammary tumours driven by a synthetic progestin combined with an oral carcinogen recapitulate several immunobiological features of human HR + breast cancers.

Some cancer cells exhibit high loads of reactive iron in lysosomes, and this feature is exploited by using fentomycin-1, a newly developed small molecule, to induce ferroptosis.

Spontaneous control of HIV is linked to the ability of CD8⁺ T cells to eliminate infected CD4⁺ T cells. Here, the authors uncover metabolic differences between HIV-specific, central memory CD8⁺ T cells from spontaneous HIV controllers and antiretrovirally treated non-controllers, and show that in vitro metabolic reprogramming enhances the antiviral response in non-controllers cells.

Secretory IgA plays vital roles interfacing between the host immune system and the resident microbiota at the mucosal surface. Here the authors explore the effect of dietary protein on the production of secretory IgA, driven by the production of extracellular vesicles by the intestinal microbiota.

X-linked myotubular myopathy (XLMTM) is a severe muscle disease with no effective treatment. Here, the authors show that tamoxifen, a drug used to treat breast cancer, rescues the pathology in a mouse model of the disease, at least in part by normalizing expression of the disease modifier proteins DNM2 and BIN1

This study identifies a novel immune checkpoint in senescent cells that is linked to the ganglioside GD3 and that contributes to the evasion of immune clearance by these cells and to aging and age-related diseases.

A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.

This study reports reduced expression of the chromatin and splicing regulator HP1γ in inflammatory bowel disease (IBD) and shows that HP1γ protects against pervasive RNA splicing leading to toxic mRNA products detected in IBD, like progerin.

Marichal and colleagues use a model of niche depletion and refilling to show that engrafted Ly6C⁺ classical monocytes proliferate locally in a Csf1 receptor-dependent manner before differentiating into lung interstitial macrophages.

The role of dietary fat vs sugar in the global obesity epidemic remains controversial. Using Nutritional Geometry methodology, the authors show that, in mice, both fats and sugars could lead to adverse metabolic outcomes, depending on the dietary context.

It is unclear why different antibiotics vary in their ability to shorten treatment of tuberculosis. Here, the authors show that a measure based on ribosomal RNA synthesis in Mycobacterium tuberculosis correlates with treatment shortening in culture, in mice and in human studies.

Defective thermogenic response to calorie overload contributes to obesity and, in foz/foz mice, to nonalcoholic steatohepatitis (NASH). Activation of brown adipose tissue function by b3AR-agonists together with moderate calorie restriction improves the obese phenotype and resolves NASH pathology. This identifies the brown adipose tissue as a target for adjuvant therapy for NASH.

Drug and target discovery for advanced liver disease are hampered by a lack of suitable models for clinical translation. Here the authors present a human liver cell-based system modeling a clinical prognostic signature allowing to propose nizatidine for treatment of advanced liver fibrosis and hepatocellular carcinoma prevention.

The prognosis of castration-resistant prostate cancers remains dismal, but accurate preclinical models can lead to effective therapies. Here the Melbourne Urological Research Alliance establish prostate cancer patient-derived xenografts, use the tumors for organoids and single-cell RNA-seq, and show the efficacy of PARP inhibitor combination treatments.

Eosinophil recruitment to the lung and intestine is regulated by type-2-innate-lymphoid-cell-derived IL-5 and IL-13; IL-5 is shown to be induced by the neuropeptide vasoactive intestinal peptide, which is known to coordinate pancreatic secretion with smooth muscle relaxation in response to feeding.

Intratumoral CD8+ T cells commonly display a dysfunctional state, however it remains unclear whether tumor cell metabolism actively promotes T-cell exhaustion. Here, the authors show that the tumor methionine recycling pathway has a central role in promoting T-cell dysfunction in hepatocellular carcinoma, contributing to tumor immune evasion.

The cGAS–STING pathway has a central role in the pathogenesis of severe COVID-19 by driving the increase in type I interferons that occurs in the later stages of SARS-CoV-2 infection.

T cells undergo metabolic reprogramming after they are activated. Rathmell and colleagues show that inflammatory Toll-like receptor signals induce glycolysis and impair the suppression of regulatory T cells, but Foxp3 can promote a switch to oxidative phosphorylation and suppression.

Anthracyclines can induce a type 1 interferon response in tumor cells that may predict clinical response to these drugs.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

In Friedreich's ataxia, caused by mutation of the gene encoding the mitochondrial protein frataxin, the major cause of mortality is heart failure. Using mice lacking frataxin in the heart, Hélène Puccio and her colleagues demonstrate that frataxin gene therapy can correct mitochondrial metabolism and reverse heart damage, raising the possibility of a gene therapy treatment for this disease.