Review Articles

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.

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.

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.

This Review from Tansey and colleagues explores how an ageing immune system, host genetics and exposure to various environmental stressors combine to promote the development of Parkinson disease.

Here, Malek and colleagues describe the multiple ways in which IL-2 biologics have been engineered to preferentially target regulatory T cells or effector T cells, memory T cells and natural killer cells to correct dysregulated or insufficient immune responses in the settings of autoimmunity or cancer.

This Review from Masters and colleagues highlights how damage to intracellular organelles is linked to activation of the innate immune system. The authors propose that a better appreciation of such organellar homeostasis could lead to the identification of novel innate immune pathways and have therapeutic implications.

Alt and colleagues review recent advances in our understanding of the mechanistic role of cohesin-mediated chromatin loop extrusion in V(D)J recombination and class-switch recombination at the immunoglobulin heavy chain locus.

Although B cells represent only a minor cell population in the central nervous system (CNS), they can contribute to CNS pathology — most notably in multiple sclerosis — through antibody and effector molecule secretion and antigen presentation. Here, Jain and Yong discuss the roles of B cells in the CNS and examine the potential for targeting these cells in various neurological conditions.

In this Review, Brian Laidlaw and Ali Ellebedy outline our current understanding of the germinal centre response in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and its importance for establishing protective immunity against the virus. They also consider the germinal centre responses seen following vaccination and how germinal centre responses may be modulated to induce broad protection against new variants of SARS-CoV-2.

Current strategies for HIV-1 cure have not been successful in eliminating the latent reservoir. This Review highlights potential therapeutic strategies that engage the immunology of dendritic cells and natural killer cells in efforts to achieve HIV-1 cure.

Studying ageing at the single-cell level has provided insight into the changes that occur systemically and in tissues as we age. For example, we now have a greater appreciation of the heterogeneity and dynamic nature of immune cell ageing and of the impact of age-associated tissue remodelling on the immune system, together contributing to increased vulnerability to some diseases.

In this Review, Manabe and Heneka examine how the systemic inflammation associated with sepsis can lead to acute cerebral dysfunction known as sepsis-associated encephalopathy (SAE). Moreover, they suggest that some of the mechanisms involved in SAE may be relevant for understanding the cognitive impairments that develop in some patients with COVID-19.

The renin–angiotensin, complement and kallikrein–kinin systems comprise a multitude of mediators that modulate physiological responses during inflammatory and infectious diseases. This Review investigates the complex interactions between these systems and how these are dysregulated in various conditions, including cardiovascular diseases and COVID-19, as well as their therapeutic implications.

Non-alcoholic steatohepatitis (NASH) is a serious chronic liver disorder of increasing prevalence worldwide. Metabolic by nature, the disease also mobilizes the immune system. Here, Huby and Gautier discuss current knowledge regarding how diverse immune cell subsets affect NASH onset and progression.

In this Review, Trim and Lynch provide an overview of the adipose tissue immune system and discuss the functional roles of adipose immune structures, as well as focusing on recently discovered ‘non-immune’ functions of adipose tissue immune cells.

This Review describes our current understanding of the functional and structural transitions that occurred during the evolution of the recombination activating gene 1 (RAG1)–RAG2 (collectively RAG) recombinase, yielding a RAG recombinase in jawed vertebrates with tightly regulated cleavage activity and strongly suppressed transposition activity.

The term ‘type I interferonpathy’ was coined 10 years ago to describe rare genetic diseases that are caused by an aberrant upregulation of type I interferon signalling. Here, Crow and Stetson discuss our current understanding of the type I interferonpathies, 10 years on.

Besides neutralizing antibodies, viruses face a range of cell-intrinsic inhibitors that are specialized to limit virus entry into host cells. Majdoul and Compton describe the mechanisms of action of the cellular factors providing this important first line of defence against virus infection, including infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).