Reviews & Analysis

This Review summarizes our current understanding of the regulation and function of mitogen-activated protein kinases (MAPKs) in innate immunity, as well as the mechanisms by which pathogens manipulate MAPK activation and the potential of targeting MAPK pathways for the treatment of inflammatory diseases.

This article describes the immunological functions of the scavenger receptors. The authors focus on the structural properties that enable these receptors to respond to a diverse range of both self and non-self ligands. They also discuss the contribution of scavenger receptors to inflammatory diseases.

Intensive research in recent years has highlighted the important and complex roles of microRNAs in the many aspects of T cell biology. In this Review, the authors describe the involvement of microRNAs in the regulatory networks that determine T helper cell fate, function and plasticity, and in the maintenance of immune tolerance.

This Review describes the recent insights that have been made from studying primary immunodeficiency diseases (PIDs). Notably, patients with gene mutations that lead to PIDs often show very different disease phenotypes from those predicted from studies of gene-deficient mice. Thus, these individuals are an invaluable resource for increasing our understanding of human immunology.

This Review describes the different types of nanotechnologies that can be used to target the immune system. The authors explain how the unique properties of different nanostructures can be used to either enhance or to suppress immune responses, and they discuss the promise of these strategies for developing more effective immunotherapies.

In this Review, the key signalling pathways that lie downstream of the pre-B cell receptor (BCR) and the BCR are discussed in terms of their contribution to B cell homeostasis and neoplasia, with a focus on the emerging distinctions between tonic and chronic active signalling.

This Review provides a comprehensive overview of very recent progress in our understanding of the role of pattern recognition receptors, including Toll-like receptors, cytosolic nucleic acid receptors and NOD-like receptors that assemble inflammasomes, in the detection of and in the defence against intracellular pathogens.

In this Opinion, the authors provide their perspective on how the type 2 immune response may have evolved and how it functions to mediate both resistance and tolerance to tissue-destructive helminths. They propose that the damage induced during helminth migration and the subsequent need for tissue repair have been major factors in driving the evolution of the type 2 response.

Dendritic cells (DCs) can promote both tolerogenic and pro-inflammatory immune responses and have been associated with various autoimmune diseases. However, it still remains unclear whether these cells have beneficial or detrimental functions in these settings. In this Review, the authors discuss the current understanding of the roles of distinct DC subsets in autoimmunity.

This article describes recent progress in delineating the factors that contribute to spontaneous HIV-1 immune control, with the ultimate aim of translating these studies into clinical strategies to induce a 'functional cure' of HIV-1 infection.

In this Review, the authors discuss the molecular mechanisms that enable B cells to internalize, process and present antigens on MHC class II molecules to CD4⁺T cells. They focus on the importance of cytoskeletal rearrangements and the establishment of polarity in B cells for these processes.

The transcription factors BATF (basic leucine zipper transcription factor ATF-like), BATF2 and BATF3 have unique positive transcriptional activities in the development and the function of dendritic cells, B cells and T cells, which are mediated through molecular interactions with interferon-regulatory factor 4 (IRF4) and IRF8.

Primary antibody deficiencies (PADs) are the most common form of hereditary immunodeficiencies. Here, the authors discuss how recent progress in the genetic and molecular understanding of PADs has illuminated previously unappreciated aspects of B cell function and has helped to explain the broad range of pathologies linked to PADs.

Coronins were first characterized on the basis of their interactions with the actin cytoskeleton and were later linked to immune dysfunction. In this short, focused Review, the authors discuss the emerging roles of coronins in immune cell signalling.

The mechanisms underlying the antiviral activity of type I interferons (IFNs) are still unclear, but IFNα has long been used in the treatment of chronic hepatitis C (CHC). While reviewing the history of IFNα-based CHC treatment, Markus H. Heim highlights the remaining questions and discusses the future challenges of IFN-based therapies.

Immune dysfunction is a recurring theme in the pathogenesis of age-related macular degeneration, which is the leading cause of blindness in aged individuals. Understanding the dual nature of ocular immune pathways in both visual homeostasis and retinal damage could aid the development of immune-based therapeutics for this disease.

Inflammasomes are multiprotein signalling platforms that activate the highly pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and induce cell death in response to pathogens and sterile stressors. This Review provides a comprehensive overview of our rapidly evolving understanding of the regulatory mechanisms that control the activation of distinct inflammasome components, as well as the non-canonical processing of IL-1β.

In this Viewpoint article, several experts share their thoughts on the plasticity and stability of regulatory T cells, discussing the recent advances in our understanding of the transcriptional and epigenetic regulation of this important T cell subset, as well as the therapeutic implications of this research.

An increasing number of studies have highlighted novel aspects of the differentiation and function of T follicular helper (T_FH) cells. Tangye et al. discuss these recent findings with a particular focus on the role of human T_FHcells in disease pathogenesis.

The past 15 years have seen a breakthrough in the field of innate immunity. In this Timeline article, the authors discuss the early events that led to the identification of Toll-like receptors as the prototype pattern-recognition receptors that link innate and adaptive immune responses.