Reviews & Analysis

Histone deacetylases (HDACs) and histone acetyltransferases mediate reversible acetylation of histones and many other non-histone proteins to regulate gene expression and protein function. Here, the authors describe the myriad activities of HDACs in CD4⁺ T cells and the potential use of HDAC inhibitors as therapeutics for immune-mediated diseases.

Here, the authors examine the functions of different subsets of invariant natural killer T (iNKT) cells. They explain how iNKT cells contribute to tissue homeostasis and protection against infection, with a focus on the liver, intestine, lungs and adipose tissue.

Lionel Ivashkiv discusses new insight into the functions of IFNγ and summarizes our current understanding of IFNγ receptor signalling. In particular, the author focuses on recent studies on how IFNγ influences autoimmunity, immunometabolism, neurological diseases and cancer immunotherapy.

Resisters are individuals who show resistance to infection despite long-term, high exposure to Mycobacterium tuberculosis. In this Review, Simmons and colleagues discuss potential mechanisms underlying this resistance, such as those mediated by macrophages, T cells and B cells, and how an understanding of these mechanisms might aid in the development of therapies for tuberculosis.

Most candidate vaccines for tuberculosis are designed to boost cell-mediated immunity to Mycobacterium tuberculosis, the intracellular bacterium that causes the disease. This Opinion article considers the rationale for also harnessing antibody-mediated immunity in future tuberculosis vaccines.

This Review discusses the latest insights into the mechanisms regulating T cell receptor (TCR) signalling responses. In particular, the authors focus on how TCR signalling is regulated during thymocyte selection and during T cell homeostasis.

Oncolytic viruses can target multiple steps in the cancer–immunity cycle and can be engineered to express therapeutic genes and, as a result, can be usefully integrated in combination tumour immunotherapies. Here, the authors discuss features of oncolytic viruses that make them appealing agents for combination approaches in cancer immunotherapy.

The intestine harbours a complex array of intraepithelial lymphocytes that patrol the epithelial layer and exert rapid cytolytic function. Here, the authors compare the different cytolytic populations and suggest that this diversity results from evolutionary pressure to protect this important barrier.

This Review considers the importance of the core circadian clock for regulating both innate and adaptive immune cell responses. The authors consider the implications for vaccination and other clinical strategies, highlighting the emerging field of chrono-immunotherapy.

This Timeline looks back at the past 60 years of fundamental research into the mechanisms of T cell-mediated cytotoxicity, which has culminated in recent interest in the therapeutic manipulation of cytotoxic T cell responses for cancer immunotherapy.

Jamie Rossjohn and colleagues review the structural and functional data that provide insight into the MHC restriction of T cell receptors. They discuss the non-mutually exclusive contributions of intrinsic germline-encoded motifs and developmental selection to MHC restriction.

Drugs that target the cytokines that drive asthma and chronic obstructive pulmonary disease offer relief to some people with these diseases. However, as discussed here, further success will require a better understanding of the disease mechanisms and selection of the right drug for the right patient.

Recently discovered roles for C-type lectins in development, homeostasis, cell death, cancer and autoimmune and inflammatory diseases extend the functions of this superfamily beyond their well-recognized involvement in antimicrobial responses.

Nonhuman primates (NHPs) are increasingly used as models of human viral infections. Here, Estes and colleagues introduce different NHP models, summarize the similarities and differences between human and NHP immune systems and discuss important examples of human viruses that can be modelled in NHPs.

Adaptive immunity arose 500 million years ago in cold-blooded vertebrates. Here, Martin Flajnik discusses how recent discoveries in fish, amphibians and reptiles have improved our understanding of the origins and functions of adaptive immune systems.

Evidence is increasing that naive T cells are heterogeneous in phenotype, function, dynamics and differentiation status. Here, van den Broek et al. provide a revised view of the naive T cell compartment and then discuss the implications for ageing, neonatal immunity and T cell reconstitution following haematopoietic stem cell transplantation.

In this Timeline, Allan Mowat reflects on some of the key discoveries that have shaped our understanding of how immune tolerance towards environmental antigens, such as commensal bacteria and food proteins, develops and is maintained in the intestine.

Could the specific glycosylation signatures associated with tumour cells be harnessed for immunotherapy purposes? In this Opinion, the authors propose that the tumour glyco-code may represent a novel immune checkpoint that could be targeted in the clinic.

In 2017, epidemiological studies in humans and experiments in mouse models showed that the intestinal microbiota determines the effectiveness of anticancer immunotherapies. As such the microbiota offers new prognostic biomarkers and shows promise as a target for future antineoplastic treatments.

CD8⁺T cell differentiation and function are regulated by epigenetic changes mainly including DNA methylation, histone modification and modification of chromatin architecture. As described here, a detailed understanding of these epigenetic mechanisms can be harnessed to improve T cell-based immunotherapies.