Comment in 2020

The similarities and differences between trained immunity and other immune processes are the subject of intense interrogation. Therefore, a consensus on the definition of trained immunity in both in vitro and in vivo settings, as well as in experimental models and human subjects, is necessary for advancing this field of research. Here we aim to establish a common framework that describes the experimental standards for defining trained immunity.

Anjana Rao describes the team effort to define the changes in chromatin accessibility in naive T cells during T_H1 and T_H2 cell differentiation after stimulation with TCR ligands and the appropriate cytokines. Her lab showed that differentiated T_H1 and T_H2 cells, which produce the cytokines IFN-γ and IL-4, respectively, displayed distinct patterns of DNase I hypersensitivity, histone acetylation and NFAT1 transcription factor binding around the Ifng and Il4 genes. This project turned them into a ‘real’ immunology lab!

Whether and how thymic tolerance to tissue-restricted antigens (TRA) could be achieved posed a conundrum until Klein and colleagues discovered that medullary thymic epithelial cells were capable of bursts of TRA expression.

Working on the function of a new cytokine always makes for exciting times. Vassili Soumelis and Yong-Jun Liu bring us back to the discovery and functional characterization of human TSLP, in the very stimulating environment of the DNAX Research Institute.

In October 2005, we, alongside the laboratory of Casey Weaver, identified a third type of helper T cells that produce the cytokine IL-17, important for the regulation of tissue inflammation.

Laurie Glimcher and colleagues recount their work that showed how the transcription factor XBP1 and the UPR signaling pathway are interconnected during plasma cell differentiation.

Casey Weaver recounts how his group’s discovery of the T_H17 pathway resolved several conundrums that had arisen in the wake of the original T_H1–T_H2 hypothesis.

Katerina Akassoglou recounts how her work on the mechanisms and functions of blood leaks in the brain led to the discovery of fibrin-targeting immunotherapy.

Frank Carbone describes how his lab identified a new class of memory T cells that permanently reside in the tissues.

Paola Ricciardi-Castagnoli describes how her groups’ focus on mucosal immunity led to the discovery of how dendritic cells sense the gut microbiota to maintain homeostasis.

Takashi Fujita’s discovery of RNA helicases as intracellular viral replication sensors illustrates how scientific knowledge develops in logical — and sometimes illogical — ways.

Nature Immunology’s 20^th anniversary is a good opportunity to reminisce about the ImmGen collective endeavor — its goals, successes and horror stories — and the group’s exploration of various modes of scientific publishing.

Fred Ramsdell and Alexander Rudensky revisit the discovery of the Foxp3 gene and its foundational role in the differentiation and function of regulatory T cells.

Immunologists used to avoid metabolism, but that is no longer possible. Now that we must talk about it, how can we do so in a way that enhances and clarifies our understanding of the role metabolism plays in the immune response?

Despite new vaccines, therapeutics, and the extensive lessons learned from the West African Ebola outbreak, the DRC’s 2018–2020 outbreak has taken nearly 20 months to bring under control. This Comment explores some of the factors that have made this outbreak so complex.

Climate change is already affecting vector-borne disease transmission and spread, and its impacts are likely to worsen. In the face of ongoing climate change, we must intensify efforts to prevent and control vector-borne diseases.

Climate change can trigger a sequence of events of significant magnitude with consequences for waterborne diseases. Heavy rainfall, flooding and hot weather are associated with waterborne diseases, but early warning systems could intercept these cascading risks.

Ann Ager is chair of its Forum and a trustee for the British Society for Immunology, and council member of the International Union of Immunological Societies. She discusses her role as an advocate for immunology to governments and other policy makers.