Perspectives

LAG-3 is a T cell inhibitory receptor with a lot of promise as a target for immunotherapy, but considerable research will be needed to fully understand the nuances of this receptor and how best to target it, as outlined in this Perspective.

Hidalgo and colleagues discuss general functional features of the neutrophil compartment that may be relevant in physiological scenarios such as specialization in naïve tissues, diversification and functional bias in inflammatory sites.

Schwartz et al. propose that the antiviral type I interferon response in the brain’s choroid plexus might lead to cognitive sequelae in COVID-19.

Halper-Stromberg and Jabri discuss the molecular and functional adaptations to inflammatory or pathogenic stimuli that shape the immune identity of each individual.

The role of eosinophils in response to cancer is not well understood. Here the authors document evidence that eosinophils contribute to the immune response to cancer and to immunotherapies and postulate that these cells might be more important than expected in these contexts.

In part of a series of commissioned pieces on coronavirus disease 2019 (COVID-19), Sekaly and colleagues discuss COVID-19 vaccine progress, the underlying biology and prospects for the future.

In this Perspective, Spaan and colleagues propose a strategy for identifying, recruiting, and genetically analyzing individuals who are naturally resistant to SARS-CoV-2 infection.

The T helper subset paradigm has been instrumental in informing our understanding of T cell diversity; however, modern single-cell analyses have revealed the limits of the concept. In their Perspective, Becher and colleagues propose an alternative framework in which to understand T helper diversity, based not on transcription factors and cytokines but rather physiological functionality.

Animal models provide invaluable insights into the functioning of the immune system; however, they have their limitations. In a Perspective, Andrea Graham argues that using a more naturalized biotic and abiotic setting can help capture a more accurate picture of the immune system.

Based on the results of recent studies that have dissected the response of individual macrophage subsets to pulmonary insults, Guilliams and Svedberg call for an adjustment of the macrophage plasticity concept.

Schwartzberg and colleagues discuss the advances and challenges for female scientists working in the field of immunology at the US NIH.

Zhu and colleagues discuss the forces that affect the ligand recognition, receptor triggering and signal transduction downstream of immunoreceptors, and their implication on lineage decision and effector function.

In this Perspective, Willcox and Willcox discuss the inherent challenges and future possibilities in identifying the ligands recognized by the γδ TCR.

O’Garra and colleagues describe the immune response to infection with Mycobacterium tuberculosis revealed through the use of transcriptomics and the value of blood transcriptional gene signatures for the diagnosis of tuberculosis.

Saphire and colleagues provide new insight into protective antibody-mediated responses to Ebola virus and how these responses could be harnessed for therapeutic intervention and vaccine strategies.

Recent decades have seen an alarming rise in the incidence of autoimmune disease. In a Perspective, Matarese and colleagues discuss the evidence showing that changes in diet and metabolic workload can account for, at least in part, rises in the frequency of autoimmune disease.

Lambrecht and Hammad discuss how microbial diversity or dysbiosis influences epithelial barrier tissues and the impact of such interactions on the development of allergic disease.

The appearance of innate lymphoid cells was a major step in the evolution of vertebrate immunity. In their Perspective, Vivier et al. survey these cells in evolution and their functional inter-relationship with conventional T cells and B cells.

The redundant or specialized roles of innate lymphoid cells (ILCs) relative to those of T cells in vivo remain hard to delineate experimentally. Bando and Colonna review the current understanding of the specialized in vivo functions of ILCs and discuss the genetic mouse models used to assess the contributions of ILCs versus those of T cells.

Bedoui and colleagues discuss the naive state of conventional T cells as an actively repressed condition that supports T cell diversity and enables the flexible differentiation of effectors, and also offers a relevant discrimination criterion between innate and adaptive lymphocytes.