Comment

Translational patient-oriented research is essential for understanding the immunopathology of SARS-CoV-2 and the varied host responses to this virus. Successful research collaborations place the patient at the center while designing the team, setting, timing, data elements and biospecimens to address important questions and advance human health.

If new treatments for immune-mediated inflammatory diseases (IMIDs) are to emerge, then a radical new approach that moves the field from one that is based on clinical signs and symptoms to one that is based on immunological and molecular mechanisms is urgently needed. This requires a new way of thinking: that IMIDs should be approached as having shared common pathogenic cells and pathways, and that therapies should be targeted at these cells and processes rather than clinical features.

High-dimensional cytometry experiments measuring 20–50 cellular markers have become routine in many laboratories. The increased complexity of these datasets requires added rigor during the experimental planning and the subsequent manual and computational data analysis to avoid artefacts and misinterpretation of results. Here we discuss pitfalls frequently encountered during high-dimensional cytometry data analysis and aim to provide a basic framework and recommendations for reporting and analyzing these datasets.

One year into the COVID-19 pandemic, governments and health agencies are hyperfocused on mitigation efforts such as masking and physical distancing, as well as vaccine logistics—as they should be. But they continue to ignore, much to everyone’s peril, a parallel, ever-worsening public health crisis: the damage done by the spread of medical mis- and disinformation online.

Different kinds of mentorship provide avenues for researchers to support the development of a more diverse and inclusive science workforce.

Ulrich von Andrian recounts how an unexpected experimental result called into question a well-established concept in immunology: the mechanism of immune memory. Follow-up experiments revealed that NK cells can mediate antigen-specific adaptive immune responses.

New Zealand has avoided the major health impacts of the SARS-CoV-2 pandemic due to a strict country-wide lockdown, the end-goal of which was elimination rather than mitigation and suppression. The New Zealand government’s use of scientific expertise, spanning public health, infectious diseases, genomics, modeling and immunology, has been one of the keys to the success of its SARS-CoV-2 elimination and control strategy.

From the onset of the SARS-CoV-2 pandemic and following the creation of the ‘Coronavirus Unit’, Argentinean scientists and technologists have contributed by leading basic and translational research initiatives, including developing diagnostic and serological kits, designing new therapeutic approaches, establishing epidemiological platforms, executing clinical trials and implementing social measures to protect the most vulnerable groups of the population.

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.