NRI at 20

As we celebrate 20 years since the launch of Nature Reviews Immunology, we reflect on how far the field of immunology has advanced over the past two decades.

Shane Crotty discusses three independent studies published in 2009 that characterized T follicular helper cells as a distinct subset of CD4⁺ T cells on the basis of selective expression of BCL6.

Max Cooper recalls the discovery of variable lymphocyte receptors in lampreys and hagfish and explains the significance of this for understanding how adaptive immunity evolved in vertebrates.

Eric Vivier describes the unexpected discovery of new populations of innate-like lymphocytes and the development of the innate lymphoid cell nomenclature.

Chen Dong provides an account of the discovery of T_H17 cells.

Derek Gilroy describes two studies that revealed an unexpected mechanism by which the resolution of inflammation can be induced.

Shohei Hori recalls the early work that led to the identification of FOXP3 as the master regulator of regulatory T cells.

Erika Pearce reflects on some of the early studies that helped to ignite the field of immunometabolism.

Feng Shao highlights the studies that led to the discovery and definition of pyroptosis as gasdermin-mediated programmed necrotic cell death.

Eicke Latz recalls the discovery of the inflammasome in 2002 and how it revolutionized our understanding of inflammation and is now a target of new immunotherapeutics for inflammatory disease.

Mihai Netea tells us how the dichotomy of innate and adaptive immunity was blurred with the description of trained immunity in 2012 — a process by which innate immune cells and their progenitors store memory of past infections by epigenetic reprogramming.

In this Journal Club, Zitvogel and Kroemer discuss a landmark study that initiated the genetic and molecular characterization of the immune–microbiota crosstalk.

Katalin Karikó describes the discovery that replacing uridine with pseudouridine renders RNA non-immunogenic. This paved the way for developing mRNA for protein replacement therapy and, surprisingly, also for mRNA-based vaccine development.

Although it was known for decades that type I interferons are crucial for antiviral immunity, it was not until the discovery of cGAS and cGAMP signalling in 2013 that we understood how cytosolic DNA induces them in infected cells, as explained by Andrea Ablasser.

Martin Guilliams and Charlotte Scott summarize some of the key studies that led to a refined dendritic cell nomenclature system based on ontogeny.

Arturo Zychlinsky and Volker Brinkman recall the discovery of neutrophil extracellular traps.

Laura Mackay highlights seminal studies that shed light on tissue immunity and the unique biology of tissue-resident memory T cells.

The early 2000s saw the first trials of checkpoint inhibitors in humans. Here, Jedd Wolchok discusses the first clinical results.

David Schneider explains the concept of disease tolerance and describes the first observations of this phenomenon in animal models.

Gwendalyn Randolph reminds us of how our view of macrophage origin and identity has drastically changed over the past 15 years.

Beth Stevens and Matthew Johnson discuss the unexpected finding that classical complement components guide synaptic pruning in the brain and are necessary for healthy brain function.

In this Perspective, Murphy and Febbraio reflect on the advances that have been made in the past 20 years in developing therapies for cardiovascular and metabolic diseases that target the immune system. They also consider the potential of emerging immune-based therapies for these diseases.

In this Perspective, McInnes and Gravallese highlight the remarkable progress made over the past 20 years in treating immune-mediated inflammatory diseases. The available therapies have progressed from broad-spectrum immune modulators to highly targeted biological and small-molecule agents as our understanding of disease mechanisms has advanced.