Reviews & Analysis

Many clinically relevant pathogens enter the body through mucosal surfaces, yet conventional parenteral immunization is insufficient to elicit robust mucosal immunity. This Review examines the unique anatomical and immunological features of the mucosal surfaces of the body and how this knowledge can be used to develop protective mucosal vaccines.

Ageing of the immune system is now realized to drive systemic ageing, and there is interest in targeting immune ageing in order to promote healthy ageing. Here, the authors detail how ageing affects different immune cell populations and discuss strategies to rejuvenate the immune system in order to extend healthspan.

Fibrosis disrupts organ function through excessive extracellular matrix deposition, particularly in pulmonary cases. Insights from single-cell sequencing reveal fibroblast heterogeneity and regulation by immunological, mechanical and metabolic factors, highlighting pathways leading to progressive fibrosis versus effective tissue repair.

JAK inhibitors are typically used to suppress the immune system but have also been shown to enhance antitumour and antiviral immune responses. In this Perspective, Zak and Teijaro explore the basis of the immune-enhancing properties of JAK inhibitors and consider whether we can exploit these properties for cancer therapy.

In this Review, Martín-Cófreces, Calzada-Fraile and Sánchez-Madrid describe the bidirectional communication that occurs at immune synapses, focusing on the crosstalk between T cells and dendritic cells. They explain how this dialogue shapes the immune functions of both interacting cell types and discuss how an improved understanding of these processes could help in the design of more effective immunotherapies.

RNA-binding proteins (RBPs) considerably expand the information content of the genome and can determine the lifespan, localization and function of RNA, thereby controlling when, where and how much protein is produced. There is a growing body of evidence that links RBPs to specialized functions of immune cells and they can also mediate cell-autonomous immunity to foreign RNA and to misfolded self-RNAs. This Review examines how RBPs regulate the biogenesis and fate of mRNAs to mediate immune cell function and cell-autonomous immunity and their roles in immunodeficiency, autoimmunity and chronic inflammation.

Certain metabolites in the tumour microenvironment signal between tumour cells and infiltrating immune cells. Here, the authors discuss how metabolites as signalling molecules function covalently and non-covalently to reshape antitumour immunity. They describe the behavioural characteristics of these metabolites and their clinical implications.

Here, Becher and colleagues examine the paradoxical roles of IL-12 and IL-23, two IL-12 family cytokines that drive type 1 and type 3 immune responses, respectively. Both promote inflammation by activating T cells, natural cells and innate lymphoid cells through cytokine polarization, yet IL-12 also supports antitumour immunity and IL-23 maintains barrier integrity. This Review highlights emerging evidence that both cytokines can also dampen immune responses, revealing unexpected regulatory roles in cancer, autoimmunity and tissue homeostasis.

This Review describes leukocyte migration through various types of extracellular matrix (ECM) during inflammation, as well as the changes to the ECM that occur in chronic inflammation and tumours. It also explores possibilities for exploiting features of the ECM for developing innovative adjunct therapies for these pathologies.

T helper 17 (T_H17) cells can have both pro-tumour and antitumour effects. Understanding how they are regulated by environmental and regulatory cues according to context will inform strategies to harness their activity for the development of next-generation cancer immunotherapies.

Ubiquitination tags proteins for proteasomal degradation but can also orchestrate the assembly of intracellular signalling platforms and direct substrates, such as damaged organelles and intracellular pathogens, for degradation by autophagy. This Review highlights the importance of these roles of ubiquitination in the context of pathogenic infection.

This Review from Turk and Huang discusses the immune processes involved in the development of vitiligo, an autoimmune disease in which melanocyte destruction causes loss of skin pigmentation. The authors highlight key studies from the past two decades that have shaped our understanding of vitiligo and led to newly approved immune-modulating drugs for the disease.

This Consensus Statement clarifies the existing subset-based nomenclature for T cells. Furthermore, it proposes an alternative modular nomenclature that is designed to be brief and flexible and to avoid ambiguity and unwanted implications. The authors also provide guidance on how T cell nomenclature should be described in research papers.

In this Review, the authors consider a long-standing immunological conundrum — why do neutrophils have a segmented nucleus? They discuss the mechanisms that may underlie segmentation of the neutrophil nucleus and explain how nuclear segmentation may affect neutrophil functions, including migration and phagocytosis.

In this Review, Li and Underhill discuss recent advances in understanding the process of phagocytosis. The authors highlight how phagocytosis is integral for innate immune sensing and explain how the phagocytosed material itself shapes the phagocytosis process.

This Perspective presents a framework of ‘structural immunity’ that positions immune cells as architects of tissue structure. Beyond their roles in antimicrobial defence, we posit that immune cells contribute to tissue homeostasis by guiding structural composition and, in some cases, directly building barrier components.

As more spaceflight missions plan to take humans back to the moon — and beyond — a key goal is to understand how spaceflight affects the immune system. In this Review, researchers from academia and international space agencies discuss the emergence of the field of ‘astroimmunology’. They outline the main immunological challenges we must overcome to facilitate safe space exploration by humans.

The tumour microenvironment (TME) poses a significant obstacle to the success of chimeric antigen receptor (CAR) T cell immunotherapy in solid tumours. Here, the authors detail how both cellular and non-cellular components of the TME contribute to tumour resistance against CAR T cell therapy, and explore emerging strategies aimed at overcoming these barriers in order to enhance the efficacy of CAR T cell therapy.

In this Review, the authors discuss the latest advances in our understanding of organelle biology in T cell-mediated antitumour immunity and how this knowledge is being used to power the next generation of cancer immunotherapy applications through pharmacological or genetic manipulation of organelles and intercellular organelle transfer or organelle transplantation.

This Review explains how an improved understanding of immune and nervous system interactions in the central nervous system (CNS) has guided the use of immunotherapies (including chimeric antigen receptor T cells, oncolytic viruses, cancer vaccines and immune-checkpoint inhibitors) to treat CNS tumours. The authors highlight the outcomes of clinical trials that have used immunotherapy to treat primary brain cancers and provide a perspective on future directions for the field.