Reviews & Analysis

Accumulating evidence suggests that environmental experiences during childhood can result in the development of allergies that persist into adulthood. In this Review, the authors present the evidence for specific early life exposures that may tip the balance between tolerance and allergic sensitization.

In this Opinion article, the authors discuss our growing appreciation of antigen-inexperienced memory T cell subsets. They focus on the development and functions of the recently described 'virtual memory' and 'innate memory' CD8⁺T cell populations, and propose a unified nomenclature for these subsets.

This Review discusses how genetically discordant microchimeric cells transferred between a mother and her offspring during pregnancy have important implications for definitions of immunological identity and tolerance.

The detection of cell wall components has a critical role in the recognition of bacteria and the initiation of host defence. In this Review, Kieser and Kagan discuss common themes associated with the detection of individual bacterial products by diverse receptors of the innate immune system.

The transcriptional repressors BTB and CNC homology 1 (BACH1) and BACH2 compete with transcriptional activators of the basic region leucine zipper (bZIP) family to control widespread functions of the innate and adaptive immune systems.

In this Opinion article, the authors discuss the limitations of categorizing tissue-resident macrophages based on their ontogeny. Instead, they propose that competition for a limited number of tissue niches may serve as a better framework for understanding the origins and functions of tissue macrophages.

Monocytes not only serve as precursors for macrophages, but also contribute to tissue immunity by presenting antigen to T cells and producing immunomodulatory mediators. In this Review, the authors discuss some of these less well-appreciated immune functions of monocytes.

Sepsis — which is caused by a dysregulated host response to infection — is a life-threatening organ dysfunction. This Review describes the recent advances in our understanding of sepsis pathogenesis and discusses strategies for the development of successful therapies.

Mitochondrial DNA (mtDNA) can engage multiple pattern-recognition receptors to trigger pro-inflammatory and type I interferon responses. This Review provides an overview of how these responses are activated by summarizing the unique features of mtDNA and how it is exposed during cellular stress.

In this Review, the authors propose that disease-associated genetic variants modulate signalling downstream of B cell receptors, Toll-like receptors and cytokine receptors in B cells to drive autoimmune responses. This altered signalling favours a naive B cell repertoire that is skewed towards self-reactivity and promotes the peripheral activation of autoreactive B cell clones.

Receptor editing and apoptosis have crucial roles in promoting the central tolerance of B cells to self-antigens. Defects of these processes can result in autoimmunity or immunodeficiency disease in humans and mice.

This Review describes the distinct mononuclear phagocyte system (MPS) cells that are found in the different compartments of the eye. The authors discuss the importance of MPS cells for maintaining tissue homeostasis and explain how these cells contribute to eye pathology following a loss of immune privilege.

The generation of a diverse T cell repertoire depends on heterogeneous populations of thymic epithelial cells (TECs). Here, the authors explain how different subsets of TECs support and coordinate different stages of T cell development to ensure the selection of a functional and self-tolerant T cell repertoire.

This Review describes the different populations of monocytes and macrophages, including Kupffer cells, that are found in the liver. The authors discuss the immune functions of these cells in the homeostatic liver as well as during liver infection and disease.

Neutrophils are rapidly recruited to tissues in response to injury or infection, and they have mainly been studied in the context of acute inflammation. However, neutrophils can also be important contributors to chronic tissue inflammation. This Review discusses neutrophil function in the context of chronic inflammation and considers the potential of targeting these cells in chronic diseases.

This Review provides an overview of the cross-presentation of antigens derived from dead cells and describes how immunological signals from dying cells influence T cell cross-priming. The authors propose a novel classification of the immunogenic signals that arise from dying cells and discuss how different forms of cell death may influence the outcome of cross-presentation.

An increasing number of multifactorial diseases have been linked to intestinal dysbiosis — that is, changes in the composition and function of the gut microbiome. Here, the authors explore the causes and consequences of dysbiosis, and discuss implications for the aetiology and treatment of many common immune-mediated diseases.

In this Review, the authors discuss the effects of glucocorticoids on both innate and adaptive immunity. They explain the mechanistic basis of glucocorticoid-mediated immunosuppression and highlight the less well-appreciated roles of glucocorticoids in enhancing immune responses.

Innate immune responses are triggered in response to the sensing of pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs). An emerging idea is that inflammasome activation may also occur independently of PRR activation following a disturbance in cellular homeostasis. The authors explore this concept and the implications for chronic inflammatory disease in this Opinion article.

In this Timeline article, Shigekazu Nagata and Masato Tanaka highlight some of the key discoveries that have shaped the field of programmed cell death over the past 50 years and explain their relevance for the immune system.