Reviews & Analysis

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.

The cell-autonomous innate immune system has long been considered an evolutionary innovation of metazoans; however, recent evidence challenges this dogma. This Perspective describes the components of antiviral immunity that are conserved from bacteria to humans, and presents potential evolutionary scenarios to explain the observed conservation.

Type 2 innate lymphoid cells (ILC2s) have diverse phenotypes across different tissues and disease states. Recent insights into ILC2 biology raise new possibilities for the improved treatment of cancer and of metabolic, infectious and chronic inflammatory diseases.

This Review discusses the immunomodulatory properties of phosphoinositide 3-kinase-γ (PI3Kγ) in health and in the context of various diseases, ranging from cardiovascular disease to auto-immunity and cancer, and discusses the therapeutic potential of PI3Kγ inhibitors, which have entered clinical trials for cancer.

In this Progress article, Male summarizes our current understanding of the risks associated with SARS-CoV-2 infection in pregnancy. Importantly, the article highlights the now substantial body of evidence supporting the safety and efficacy of COVID-19 vaccination in pregnancy.

To realize the full potential of genetic engineering of haematopoietic stem cells for a broad range of clinical indications, substantial immunological challenges must be overcome. These include innate and adaptive immune responses to gene-therapy reagents and adaptive immune responses to neoantigens expressed by genetically engineered cells.

The authors of this Review discuss the current evidence suggesting that pathological immune activation contributes to irritable bowel syndrome (IBS). They explain how immune mediators can contribute to pain signalling and abdominal pain, and highlight the potential for targeting immune pathways in IBS.

In this Perspective, Amersfoort, Eelen and Carmeliet discuss emerging evidence for tissue- and vessel type-specific immunomodulatory roles of distinct subtypes of endothelial cells, which they collectively refer to as ‘immunomodulatory endothelial cells’ (IMECs).

Individuals with autoimmunity often have an increased frequency of T cells bearing features of follicular helper T cells in their blood. Lucy Walker proposes that alterations in pathways that regulate autoimmunity are coupled to alterations in follicular helper T cell homeostasis.