Review Articles in 2016

Understanding how decoy receptors for cytokines and chemokines work requires in-depth insights into their structure. In this Review, the authors provide a structural overview of both mammalian and viral decoy receptors and highlight opportunities for leveraging their immunomodulatory activity for therapeutic purposes.

In this Review, the authors summarize recent findings that illustrate the emerging roles of CCCH zinc finger proteins, which are involved in the regulation of multiple steps of RNA metabolism, in the regulation of immune responses including cytokine production, immune cell activation and immune homeostasis.

Understanding the gradual development of disease in patients with seropositive rheumatoid arthritis offers new opportunities for prevention and early therapy.

This Review discusses the contribution of different cytokine networks to inflammation in the central nervous system (CNS). In neuroinflammatory diseases such as multiple sclerosis, CNS-invading leukocytes produce many of the cytokines that are associated with disease. By contrast, in Alzheimer disease and other neurodegenerative diseases, tissue-resident cells are the main source of pathological cytokines.

This Review provides a comprehensive overview of the influences on human immune system variation. Systems immunology analyses have revealed that variations between individuals are mainly due to non-heritable influences such as age, sex, microbiota and the environment.

Dendritic cells (DCs) shape tolerogenic and pro-inflammatory immune responses by presenting antigens to T cells; their ability to localize in peripheral tissues and secondary lymphoid organs is crucial for these functions. This Review describes the different migratory pathways employed by subsets of DCs from distinct tissue sites, detailing their mechanistic basis and importance for maintaining health.

This Review provides a comprehensive overview of the early airway immune responses to infections. The authors discuss the stepwise engagement of distinct tiers of effector functions and how early airway immune responses are influenced by factors such as the environment, obesity and ageing.

In this Review, the authors discuss the emerging roles for members of the transforming growth factor-β (TGFβ) superfamily in regulating immune responses. In particular, they focus on how activin A and bone morphogenetic proteins (BMPs) regulate innate and adaptive immune cells in inflammatory diseases and cancer.

Research into the immune mechanisms associated with healthy tolerance to common foods, the inflammatory response underlying food allergies, and immunotherapy-induced desensitization promises new approaches to the diagnosis, prevention and treatment of food allergy.

Initiation of an adaptive immune response depends on the detection of both antigenic epitopes and adjuvant signals. Infectious pathogens and cancer cells often avoid immune detection by limiting the release of danger signals from dying cells. When is cell death immunogenic and what are the pathophysiological implications of this process?

This Review describes the major lipid species found in the plasma membrane of mammalian cells and highlights the importance of these lipids for regulating T cell signalling. Recent studies have shown that drugs modulating the membrane lipid composition in T cells can alter their immune functions — the authors discuss the potential for such lipid-based immunotherapies in autoimmunity and cancer.

This article provides a comprehensive overview of the general functions of autophagy in immunity, the interactions between autophagy and immune signalling pathways and the role of autophagy–immune crosstalk in multicellular immune responses and disease.

The tumour suppressor p53 has well-known functions in cell repair and cell death that have led to its title as the 'guardian of the genome'. Here, the authors discuss the less-well appreciated roles of p53 and other tumour suppressor genes in shaping immune responses; they propose that these genes could also be considered to be 'guardians of immune integrity'.

The cytokine interleukin-33 was first identified as an inducer of type 2 immune responses. It has now been shown to have pleiotropic activities on multiple immune cell types and is involved in numerous infectious and inflammatory diseases, as described in this Review.

Gain- and loss-of-function mutations in phosphoinositide 3-kinase-δ (PI3Kδ) result in a primary immunodeficiency syndrome termed APDS. Understanding the function of PI3Kδ in adaptive immune responses — from studies of mouse models of these mutations and from patients with APDS — provides new insights on how mutations in PI3Kδ promote immunodeficiencies.

This Review discusses our current understanding of the development and functions of follicular helper T (T_FH) cells. The author explains how these cells do not fit with the classical instructional model of helper T cell differentiation and, instead, proposes a model of default T_FHcell development with inherent spatiotemporal stochasticity.

In this Review the authors discuss some of the key differences that exist between male and female immune functions. They explain how these differences lead to sex biases in susceptibility to infections, inflammatory diseases and cancer. Moreover, they highlight the urgent need for immunologists to consider these sex differences when designing experiments.

In this Review, the authors summarize the features and the molecular drivers of T cell dysfunction in cancer and compare these with dysfunctional T cells in chronic viral infection. The metabolic competition in the tumour microenvironment is also discussed. Understanding antitumour T cell responses has important implications for cancer immunotherapy.

This Review describes the unique properties of mucus and mucins, with a focus on the intestine. Mucus and mucus-producing goblet cells contribute to our innate immune defences and, in turn, are regulated by the immune system. The authors discuss the link between defective mucus production and increased susceptibility to infection and inflammatory disease.

Plants depend on cell-autonomous innate immune mechanisms for protection against infection and these pathways are activated in response to pattern recognition receptor (PRR) engagement. However, as is the case in mammals, PRR signalling in plants must be tightly controlled to avoid pathological outcomes; this Review focuses on the mechanisms that regulate plant PRR signalling.