Articles in 2019

This Review presents evidence that supports a role for the immune system in the pathogenesis of hypertension, including the immune cell subsets involved and the means by which these immune cells become activated throughout the course of the disease.

Here, Ho and Kupper detail how T cell responses are generated and maintained in skin. They discuss how the various subsets of skin-resident T cells — including memory and innate-like populations — contribute to inflammatory skin disorders.

This study identifies a role for group 3 innate lymphoid cells in IL-2 production in the small intestine to maintain intestinal homeostasis through effects on regulatory T cells.

During inflammation, IL-17 rewires metabolic processes in lymph node fibroblastic reticular cells, thereby supporting their survival and population expansion.

Liver macrophages produce the non-inflammatory factor IGFBP7, which has direct effects on liver metabolism in metabolic disease without requiring a switch to a pro-inflammatory phenotype.

Tumour cells induce membrane cholesterol efflux from macrophages, leading to macrophage acquisition of a pro-tumour phenotype.

A new study shows that immune activation after infection involves competition for energy with physiological programmes such as maintaining a normal body temperature. This trade-off favours immune tolerance as a strategy for host defence.

John Harty and colleagues explain how different subsets of CD4⁺ T cells, CD8⁺ T cells and γδ T cells respond to the Plasmodium parasites that cause malaria. They discuss the major challenges that need to be overcome in order to harness T cell responses for malaria vaccines and therapies.

Doreen Cantrell describes a 2005 paper by Graham Hardie and colleagues showing that Ca²⁺–calmodulin-dependent protein kinase kinases could phosphorylate and activate AMPK, which suggested a biochemical link between T cell receptor signalling and ATP production.

Some immune cells undergo processes that pose unique challenges to the 3D organization of their genomes. These include antigen receptor rearrangement, clonal expansion and the contortion of their nuclei. Here, Allan and colleagues discuss the latest insights into these processes from a structural genomics perspective.

This Review describes the diverse and dynamic chromatin modifications that ensure rapid and appropriate innate immune responses to infection. It also discusses how pathogens themselves modify host responses through epigenetic mechanisms to evade elimination.

Lifestyle-associated pathologies have reached epidemic proportions and urgent action is needed to protect the public from unhealthy diets. Here, the authors describe how the Western diet has long-lasting effects on the immune system that promote chronic metabolic inflammatory diseases.

B cells have many unique metabolic features. Markus Müschen highlights these in this Opinion article and proposes the concept of three key metabolic gatekeepers that protect against B cell-associated autoimmunity and lymphomas.

This Review considers the link between pain and the immune system. Nociceptors are directly activated by immune mediators and microbial products and, in turn, release neuropeptides that shape immune responses. These neuroimmune pathways can contribute to protective immunity from infections but also lead to chronic pain.

Failure of anticancer immune responses is often due to T cell dysfunction, but the molecular mechanisms underlying this are incompletely understood. Two papers in Nature now identify NR4A transcription factors as key drivers of T cell dysfunction.

The intestinal microbiota profoundly shapes host physiology through its production of small molecules and metabolites. Here, Honda and colleagues discuss how these microbial products shape immune function. They further consider the potential of ‘mining’ the microbiota for new microbial and metabolite-based immunotherapies.

Mala Maini describes a 1996 paper by Frank Chisari and colleagues that showed CD8⁺ T cells can exert potent antiviral efficacy against hepatitis B virus without lysing infected cells, through the production of antiviral cytokines.

Here, the authors explore how the transcription factor T-bet shapes innate and adaptive immune responses during infection. They consider the evolutionary relationship between T-bet and the related transcription factor eomesodermin (EOMES) and explain how T-bet controls the development of effector and memory T cell populations that mediate protective immunity.

Pancreatic ductal adenocarcinoma cells induce macrophage production of pyrimidines that mediate tumour cell resistance to chemotherapy.