Reviews & Analysis

The vasculature that forms in tumours and supports tumour growth is abnormal and limits T cell entry into tumours. Here, the authors review how the tumour vasculature acts as a barrier to effective antitumour immunity and the therapeutic strategies to overcome this.

In this Review the authors explain how different routes of exposure to food antigens can contribute to the development of food allergies. They discuss how allergic sensitization occurs against food antigens and focus on how IgE and mast cells ultimately drive the allergic pathology.

During pregnancy, innate immune mechanisms at the maternal–fetal interface are important for protecting the developing fetus from pathogens. However, excessive immune activation can be harmful to the fetus, and these pathways must be properly regulated. Here, the authors discuss the growing understanding of the unique innate immune pathways that operate in the maternal and fetal compartments of the placenta.

Iron is crucial for cellular metabolism, but its availability varies greatly within and between individuals and populations. This Review highlights how iron regulates innate and adaptive cellular and humoral responses affecting protection against infections, tumours and autoimmunity.

T cells have an essential role in immune responses to Mycobacterium tuberculosis, but the mechanisms by which they may provide protective immunity remain poorly understood. This Review explores the knowns and unknowns of T cell immunity in tuberculosis and how recent technologies may inform the design of T cell-targeted TB vaccines.

This Perspective explores how the gut microbiota influences the function and heterogeneity of microglia, highlighting their roles in neurological and neuropsychiatric disorders, and discusses the therapeutic potential, challenges and clinical implications of targeting microbiota–microglia interactions.

Macrophages are crucial regulators of fibrosis. Here the authors describe how distinct subsets of monocytes and macrophages cooperate with fibroblasts across tissues to control progression from inflammation to fibrosis.

Pattern recognition receptors (PRRs) are typically associated with innate immune activation, but there is an emerging subset of inhibitory pattern recognition receptors (iPRRs) that limit cell activation. This Review from Meyaard and colleagues highlights our growing understanding of iPRR biology, focusing on leukocyte-associated immunoglobulin-like receptor (LAIR1).

In vivo chimeric antigen receptor (CAR) engineering has emerged as a promising off-the-shelf therapeutic approach for hard-to-treat diseases such as solid tumours, offering key advantages such as streamlined production, the elimination of patient-specific manufacturing, reduced costs and simplified logistics. In this Review, Yang and colleagues provide an overview of current in vivo CAR engineering strategies, highlighting existing challenges and discussing future directions for the field.

In this Perspective, Smyth and Kipnis reappraise the concept of immune privilege in the central nervous system. Although immune privilege was originally thought to involve isolation of the central nervous system from the peripheral immune system, the authors argue that it is instead a special immunological state that involves continuous neuroimmune dialogue.

Cytotoxic T lymphocytes and natural killer cells destroy target cells using a mechanically active cytolytic immune synapse. This Review examines the various ways in which mechanical forces contribute to the potency, specificity and overall efficacy of the cytotoxic response.

In this Perspective, Feuerer and colleagues consider how transposable elements (TEs) — which are mobile nucleic acid sequences in the genome — can impact diverse immune responses. For instance, transcription of TEs can activate innate immune pathways that generate type I interferons, TEs can regulate gene expression in immune cells and TEs could potentially be targeted to generate tumour neoantigens for immunotherapy purposes.

In this Review, Male and Jones provide an overview of the current vaccines that are offered during pregnancy and to newborns, explaining the rationale behind the different vaccination programmes and the unique challenges that come with immunizing these populations.

In this Review, Tse-Kang, Wani and Pukkila-Worley discuss how nematodes, such as Caenorhabditis elegans, rely on ‘patterns of pathogenesis’ as opposed to the sensing of specific ligands by pattern-recognition receptors to activate innate immune responses. They explain why this approach to immune surveillance is beneficial to C. elegans and consider how studies in C. elegans can inform our understanding of mammalian immunity.

In this Review, Kato and Kita discuss the complex interactions between airway epithelial cells and immune cells that contribute to the development of asthma and chronic rhinosinusitis. They highlight recent advances in understanding the clinical heterogeneity of these diseases and explain the progress that has been made in developing new therapies.

Beyond exhaustion, CD8⁺ T cells can adopt various dysfunctional states, including tolerant, anergic, senescent, ignorant and dying states, that compromise their ability to eradicate viruses or tumours. Here, the authors describe how these states may be distinguished, how they arise and the implications for immunotherapy.

Regulatory T (T_reg) cells have an important role in the maintenance of immune tolerance and continuously circulate in the body. During this migration, they engage in bidirectional crosstalk with lymphatic and blood endothelial cells, which regulates vascular permeability and determines T_reg cell migration patterns and tissue residency. This Review examines the molecular mechanism of these interactions and how they could be targeted in the context of autoimmunity, transplantation and cancer.

Immunoglobulins sample vast swathes of primary sequence and conformational space to generate and select B cell clones with exquisite selectivity and affinity for specific antigens. This Perspective article examines the interplay between antibody diversification mechanisms and highlights the importance of constant regions in influencing the specificity and functionality of individual antibodies.

In this Review, the authors explain how post-translational protein modification by the small ubiquitin-like modifier (SUMO) family is emerging as an important regulator of immune cell function. Notably, inhibition of sumoylation is showing promise as a cancer therapy and may also have therapeutic use in various autoimmune conditions.

New immunotherapies have the potential to mediate a sustained remission from certain autoimmune diseases. This has been referred to as achieving an ‘immune reset’ in patients. Here, Junt and colleagues discuss how we can most accurately define the term immune reset and explain the challenges in identifying suitable biomarkers of long-term disease remission.