Volume 21 Issue 10, October 2021

The cover of this issue celebrates the 20th anniversary of Nature Reviews Immunology. See Editorial

Cover design: Simon Bradbrook

Editorial

Immune discovery aplenty at twenty

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.

Collection:

NRI at 20
Editorial 27 Sept 2021
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Research Highlights

Entering the neutrophil trap

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

Volker Brinkmann
Arturo Zychlinsky

Collection:

NRI at 20
Journal Club 27 Sept 2021
Commensals shape the immune system

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

Laurence Zitvogel
Guido Kroemer

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NRI at 20
Journal Club 27 Sept 2021
The discovery of innate lymphoid cells

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

Eric Vivier

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NRI at 20
Journal Club 27 Sept 2021
Which came first, T cells or B cells?

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.

Max Cooper

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NRI at 20
Journal Club 27 Sept 2021
Revealing T follicular helper cells with BCL6

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.

Shane Crotty

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NRI at 20
Journal Club 27 Sept 2021
Lymphocytes in lockdown

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

Laura K. Mackay

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NRI at 20
Journal Club 27 Sept 2021
Defining the T_H17 cell lineage

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

Chen Dong

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NRI at 20

T cells
Journal Club 27 Sept 2021
FOXP3 as a master regulator of T_reg cells

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

Shohei Hori

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NRI at 20
Journal Club 27 Sept 2021
Metabolism as a driver of immunity

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

Erika L. Pearce

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NRI at 20
Journal Club 27 Sept 2021
Modified uridines are the key to a successful message

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.

Katalin Karikó

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NRI at 20

Nobel Prize in Physiology or Medicine 2023
Journal Club 27 Sept 2021
A billion-year-old mechanism of innate immunity uncovered

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.

Andrea Ablasser

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NRI at 20
Journal Club 27 Sept 2021
Resolving inflammation

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

Derek W. Gilroy

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NRI at 20
Journal Club 27 Sept 2021
Gasdermins: making pores for pyroptosis

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

Feng Shao

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NRI at 20
Journal Club 27 Sept 2021
Checkpoint blockade: the end of the beginning

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

Jedd D. Wolchok

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NRI at 20
Journal Club 27 Sept 2021
The inflammasome: from bench to bedside

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.

Eicke Latz

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NRI at 20
Journal Club 27 Sept 2021
The epigenetic ghost of infections past

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.

Mihai G. Netea

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NRI at 20
Journal Club 27 Sept 2021
The conventional dendritic cell lineage is born

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

Martin Guilliams
Charlotte L. Scott

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NRI at 20
Journal Club 27 Sept 2021
Immunology’s intolerance of disease tolerance

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

David S. Schneider

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NRI at 20
Journal Club 27 Sept 2021
The complement cascade repurposed in the brain

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.

Beth Stevens
Matthew B. Johnson

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NRI at 20

Neuroimmunology
Journal Club 27 Sept 2021
Tissue macrophages break dogma

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

Gwendalyn J. Randolph

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NRI at 20
Journal Club 27 Sept 2021

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Progress

Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape

This Progress article provides an update on the COVID-19 vaccine effort in the light of ongoing vaccine efficacy studies and real-world data on vaccine effectiveness, including the impact of virus variants of concern and challenges for global deployment.

John S. Tregoning
Katie E. Flight
Benjamin F. Pierce

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COVID-19 Watch

Nobel Prize in Physiology or Medicine 2023
Progress 09 Aug 2021

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Reviews

A guide to interrogating immunometabolism

This Review from Jeff Rathmell and colleagues serves as a guide to immunologists on how to select the appropriate tools and techniques to interrogate metabolism in their experimental systems. The authors provide advice for avoiding common mistakes and on how best to employ metabolomics.

Kelsey Voss
Hanna S. Hong
Jeffrey C. Rathmell
Review Article 15 Apr 2021
The inflammatory pathogenesis of colorectal cancer

Mark Schmitt and Florian Greten describe the mechanisms by which chronic inflammation can initiate tumorigenesis and by which tumour-elicited and therapy-induced inflammation can promote colorectal cancer, as well as the role of extrinsic factors such as diet, the microbiota and the mycobiota.

Mark Schmitt
Florian R. Greten
Review Article 28 Apr 2021

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Perspectives

Immune-based therapies in cardiovascular and metabolic diseases: past, present and future

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.

Andrew J. Murphy
Mark A. Febbraio

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NRI at 20
Perspective 20 Jul 2021
Immune-mediated inflammatory disease therapeutics: past, present and future

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.

Iain B. McInnes
Ellen M. Gravallese

Collection:

NRI at 20
Perspective 13 Sept 2021

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Volume 21 Issue 10, October 2021

Editorial

Immune discovery aplenty at twenty

Research Highlights

Entering the neutrophil trap

Commensals shape the immune system

The discovery of innate lymphoid cells

Which came first, T cells or B cells?

Revealing T follicular helper cells with BCL6

Lymphocytes in lockdown

Defining the T_H17 cell lineage

FOXP3 as a master regulator of T_reg cells

Metabolism as a driver of immunity

Modified uridines are the key to a successful message

A billion-year-old mechanism of innate immunity uncovered

Resolving inflammation

Gasdermins: making pores for pyroptosis

Checkpoint blockade: the end of the beginning

The inflammasome: from bench to bedside

The epigenetic ghost of infections past

The conventional dendritic cell lineage is born

Immunology’s intolerance of disease tolerance

The complement cascade repurposed in the brain

Tissue macrophages break dogma

Progress

Progress of the COVID-19 vaccine effort: viruses, vaccines and variants versus efficacy, effectiveness and escape

Reviews

A guide to interrogating immunometabolism

The inflammatory pathogenesis of colorectal cancer

Perspectives

Immune-based therapies in cardiovascular and metabolic diseases: past, present and future

Immune-mediated inflammatory disease therapeutics: past, present and future

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