Review Articles in 2016

A substantial proportion of our genome is composed of endogenous retroelements of viral origin. Such elements can retain viral characteristics and drive activation of the immune system; this can contribute to both undesirable outcomes, such as autoimmune disease, as well as beneficial responses, such as increased immune reactivity to tumours. In this Review, the authors describe the pros and the cons of these 'enemies within'.

The wide diversity of clinical and immunological phenotypes of patients with RAG deficiency, combined with structural characterization of the RAG protein complex, have provided new mechanistic insights into RAG protein function.

Autoimmune regulator (AIRE) is best known for its role in immune tolerance. In this Review, the authors summarize the recent advances in our understanding of the diverse functions of AIRE, including its role in selection of regulatory T cells and modulation of non-autoimmune diseases.

Anecdotal reports of HIV-infected children who have continued to control viral replication after discontinuing antiretroviral therapy have led to the hope that unique factors associated with paediatric infection might offer greater potential for HIV cure in children than in adults.

This Review focuses on how purinergic signalling pathways regulate both innate and adaptive immune responses. The authors discuss the potential of targeting purinergic signalling pathways for the treatment of ischaemia, organ transplantation, autoimmunity and cancer.

Enteric bacterial infections are a major cause of morbidity and mortality. In this Review, the authors describe the different types of mucosal defences — including innate and adaptive immune cells, epithelial cells and commensal microorganisms — that protect us against bacterial pathogens in the intestines.

The targeting of immunoglobulin loci by activation-induced cytidine deaminase (AID) is essential for generating a diverse antibody repertoire. However, AID also has off-target activity in B cells that can lead to oncogenic transformation. Here, the authors review recent advances in our understanding of the mechanisms that drive AID promiscuous activity.

T cells are inherently flexible and can acquire distinct functions to combat different pathogens or changing circumstances. However, this flexibility can be deleterious or advantageous depending on the disease setting. Here, the authors describe the molecular mechanisms that regulate CD4⁺T cell plasticity and how it might be harnessed to treat disease.

This Review focuses on our growing understanding of immunological memory behaviour in natural killer (NK) cells. The authors discuss the development and functions of memory NK cells and consider the potential of targeting these populations for vaccination or therapeutic purposes.

The development and maintenance of protective CD8⁺ T cell memory require help. This is provided by CD4⁺ T cells in many ways. Here, the authors review the latest insights into this multifaceted role for CD4⁺T cells, and the implications for vaccine design and T cell-based therapies.