Review Articles in 2021

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).

Kolkhir and colleagues discuss how therapies targeting human mast cells in both allergic and non-allergic disease settings have provided crucial insights into the functions of these cells.

The causative mechanisms of cachexia, a complex catabolic syndrome that can occur in the context of malignant or infectious diseases, are poorly understood. This Review examines the immunological context of cachexia and explores immunometabolic crosstalk both upstream and downstream of tissue catabolism.

CD8⁺ tissue resident memory T cells (T_RM cells) are essential for defence against pathogens and malignancies. Prior work had indicated that these cells form within inflamed tissue, but there is emerging evidence that a pool of T_RM cell precursors exists within the circulation. This Review examines the processes and signals within the lymphoid compartment that determine lineage decisions towards the formation of T_RM cells.

Atherosclerosis involves a maladaptive inflammatory response. This Review summarizes the contributions of key innate and adaptive immune cell subsets and describes diverse mechanisms that regulate their activation. It also discusses the feasibility of developing immune-targeted interventions, such as tolerogenic vaccines.

Here, Ed Lavelle and Ross Ward discuss the unique aspects of mucosal immunity that must be considered when developing effective mucosal vaccines. The authors highlight the key immune cell populations that are targeted by mucosal vaccination strategies and explain how innovative adjuvant and delivery approaches should lead to new vaccines for infectious diseases and cancers.

Activation of nucleic acid-sensing Toll-like receptors is finely tuned to limit self-reactivity while maintaining recognition of foreign microorganisms. The authors describe recent progress made in defining the regulatory mechanisms that facilitate this delicate balance.

CD8⁺ T cells assume various dysfunctional states during tumorigenesis. Here, the authors describe mechanisms of T cell dysfunction in tumours, and what determines T cell responsiveness and resistance to immunotherapy.

Neutrophils are much more than just primary responders in infection. They influence tumour development and growth in many positive and negative ways. A growing appreciation of their diversity and plasticity is revealing their complex contributions to cancer depending on time, place and disease context.

This Review discusses the immunomodulatory effects of radiotherapy on both the tumour microenvironment and surrounding healthy tissue. The authors explain how radiotherapy can cause chronic inflammation and organ dysfunction in patients, and, in particular, they consider the impact of radiotherapy-induced immune effects in the lungs and intestine.