Research Highlights in 2019

Somatic mutations conferring resistance to IL-17A-mediated apoptosis accumulate in the inflamed epithelium of patients with ulcerative colitis.

The design of vaccines that induce broadly neutralizing antibodies (bnAbs) to HIV is extremely challenging. Two reports now demonstrate strategies for the design of immunogens that can induce the production of bnAb precursors and guide these towards the acquisition of improbable mutations.

Overexpression of JUN by CAR T cells renders them resistant to exhaustion and improves tumour control in mouse models, including of solid tumours and of tumours with low levels of antigen expression.

A trispecific antibody that provides T cell co-stimulation shows promise in preclinical models of myeloma.

Endogenous oxidized phospholipids can induce a hypermetabolic state in macrophages, involving both oxidative phosphorylation and aerobic glycolysis, that boosts the inflammatory response to lipopolysaccharide.

Activated CD8⁺ T cells adapt to glutamine blockade through upregulation of acetate metabolism, whereas cancer cells lack this flexibility and are highly susceptible to glutamine blockade.

The benefits of exercise reach the bone marrow, altering haematopoietic cell niches and regulating inflammatory cell output.

Chen Dong and colleagues describe a positive-feedback loop between TOX2 and BCL-6 that helps to drive the development of T follicular helper cells in germinal centres.

Commensal human papillomaviruses prime CD8⁺ T cells that can protect against skin cancer.

Stress-induced metabolic changes in CD4⁺ T cells linked to anxiety-type behaviours.

Commensal viruses in the intestine support the proliferation and survival of intraepithelial lymphocytes through RIG-I-dependent IL-15 production and therefore contribute to healthy gut homeostasis.

Collaboration is key when it comes to mounting an effective T cell response against cancer. A new study shows that CD4⁺ T cell activation in a tumour is required to support effective priming and cytotoxic activity of tumour-infiltrating CD8⁺ T cells.

This study sheds light onto the processes by which naive T cells are preconditioned for tissue residency.

IL-17-producing γδ T cells in the meningeal spaces support short-term spatial memory formation.

A new study has identified genetic variants of the anti-inflammatory signalling molecule A20 that can be traced back to archaic humans and affect microbial resistance versus tolerance.

Two new studies define the liver-derived signals that promote Kupffer cell development from a common monocyte precursor.

This study investigates the roles of mutational burden and clonal heterogeneity in immune responses to melanoma and finds that low tumour heterogeneity is a predictor of favourable responses to immunotherapy.

Two papers by Gregory Barton and colleagues identify distinct UNC93B1-dependent mechanisms for regulation of the endosomal nucleic acid-sensing TLRs, TLR7 and TLR9.

Chimeric antigen receptor (CAR) T cells directed at fibroblast activation protein show efficacy in mouse models of hypertensive cardiac injury and fibrosis.

Antibiotics can impair the development of immunity against seasonal influenza virus in individuals with low levels of pre-existing immune memory.