Reviews & Analysis

Three-dimensional (3D) genome organization has emerged as an important regulator of gene expression and genomic interaction. Here, the authors explain how 3D genome organization impacts immune cell development and function, and discuss how aberrant genome folding can contribute to immune-mediated disease and cancer.

In this Review, Ng and colleagues examine the clinical, epidemiological and immunological aspects of monkeypox virus (MPXV) infections, with a focus on mechanisms of host immunity to MPXV. The authors also consider the unique epidemiological and pathological characteristics of the current non-endemic outbreak of the virus and discuss vaccines, therapeutics and outstanding research questions.

This Review considers how the biophysical properties of a tissue are able to shape immune cell function through the process of mechanotransduction. There are multiple mechanotransduction pathways that operate in immune cells and the authors highlight these and the emerging field of mechanoimmunology.

There are many reasons why the development of a potent and durable vaccine to HIV-1 is exceptionally challenging, including the large genetic diversity of the virus and its complex mechanisms of immune evasion. In this Review, Haynes et al. discuss strategies for the induction of potent broadly neutralizing antibodies for HIV-1 and the steps that may be necessary for ultimate success.

Here, the authors consider our emerging understanding of COVID-19-associated coagulopathy. They focus on the complex interactions between innate immune, coagulation and fibrinolytic pathways that can lead to potentially life-threatening thrombosis following SARS-CoV-2 infection.

Extracellular vesicles (EVs) are increasingly recognized as having ubiquitous roles in the immune system. This Review focuses on the progress made in the field in the past 5 years, including the roles of EVs in innate and adaptive immunity and their potential use in diagnosis and therapy.

Lorenzo Galluzzi and colleagues discuss the molecular mechanisms through which mitochondrial dysfunction elicits inflammatory reactions, the cellular pathways that are in place to control them and how the dysregulation of these systems contributes to pathology.

In this Review, Gorbunova and colleagues discuss the links between DNA damage, inflammation and ageing. They focus on the implications for premature ageing syndromes and multiple age-related diseases, and highlight potential therapeutic targets.

IL-17 cytokines drive biological responses that protect the host against many infections but can also contribute to host pathology in the context of infection and autoimmunity. Here, Kingston Mills highlights the different cellular sources of IL-17 and compares the pathological versus protective functions of these cytokines.

In early 2022, staff from the NIAID at the NIH organized a workshop focusing on the innate immune response to SARS-CoV-2. In this Viewpoint article, some of the organizers and invited speakers share their thoughts on key outcomes of this meeting.

Myeloid cells contribute to the immunosuppressive tumour microenvironment and can be responsible for resistance to cancer immunotherapy. Here, the authors describe the current therapies that aim to modulate the functional activities of myeloid cell populations, impacting their recruitment, survival and activity in the tumour microenvironment, acting at the level of cell surface receptors, signalling pathways, epigenetic machinery and metabolic regulators.

In this Perspective, the authors reflect on the historical development of host-directed immunotherapeutic interventions for viral and bacterial infections, and then focus on how historical insights can be applied to current approaches to therapy of SARS-CoV-2 and Mycobacterium tuberculosis infections.

The cytokine thymic stromal lymphopoietin (TSLP) has pleiotropic functions beyond allergic diseases and T helper 2-type immune responses. Here, the authors highlight the roles of TSLP — beneficial or deleterious — in infectious disease, chronic inflammatory disease and cancer by acting on many different cell types.

This Review explains how natural killer (NK) cells promote immunity to tumours. The authors cover the therapeutic approaches that are being developed to mobilize NK cells in patients with cancer, including NK cell activators, checkpoint blockade, cellular therapies, and bispecific and trispecific NK cell activating antibodies.

Mast cells are complex immune cells with varied functions. This Perspective explores the divergent phenotypes and functions of mast cells resulting from both their hard-wired ‘nature’ defined by their ontogeny and the ‘nurture’ they receive within specialized tissue microenvironments.

Patients with autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. This Review explores how the gut microbiota influence autoimmune responses in extra-intestinal autoimmune diseases and discusses potential preventative and therapeutic strategies targeted at the microbiota–immune interface.

Improving on current cancer immunotherapies will require engaging immune effectors beyond T cells alone. Predator–prey theory can reveal understudied and counterintuitive facets of antitumour immunity, inspiring new approaches to manipulate the tumour ecosystem in favour of cancer cell extinction.

This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

Understanding of the role of T cells in SARS-CoV-2 infection is of great importance for the design of next-generation vaccines. In this Perspective, Davenport and colleagues discuss the challenges in determining a causal relationship between vaccine-induced T cell immunity and protection from COVID-19.

This ‘guide to’ article provides an overview of the antigen processing and presentation pathways, which lead to the loading of antigenic peptides on major histocompatibility complex (MHC) molecules for detection by T cells.