Opinion in 2014

The discovery that patients with asthma can be dichotomized according to levels of type 2 inflammation, and hence their response to inhibitors of this pathway, promises to enhance our understanding of pathogenic mechanisms and personalized therapies.

The recent realization that the airways harbour a steady-state microbiota necessitates a shift in our understanding of respiratory health and disease, drawing from similarities with host–microorganism relationships in the intestines.

Recent studies have shown that complement activation is not confined to the serum but also occurs within cellular compartments. This has led to an emerging understanding that complement components can intersect diverse cellular metabolic and effector pathways. Here, the authors propose that the different locations of complement activation dictate its diverse functions.

This Opinion article proposes that higher-order protein complexes — referred to as supramolecular organizing centres (SMOCs) — form on specific organelles by nucleated polymerization downstream of innate immune receptors to amplify the signal and reach a response threshold.

In this Opinion article, the authors discuss how the induction of regulated cell death and inflammatory pathways may lead to an auto-amplification loop that causes tissue damage and organ failure. They propose that targeting both processes could be useful for treating a broad range of clinical conditions with an inflammatory basis.

Chronic viral infections and malignant tumours are associated with the development of T cells that have an 'exhausted' phenotype and that are thought to be severely functionally impaired. In this Opinion article, the authors propose that the exhausted phenotype is actually a functional adaptation to cause minimal tissue damage while still mediating a critical level of pathogen control.

Reiner and Adams propose a deterministic scenario for diversifying the fates of the cellular progeny of a single antigen-selected lymphocyte, with an element of plasticity based on the nature of the pathogen and the number of responding cells.

Studies in mice indicate that targeting antigens to dendritic cells (DCs) can elicit strong CD4⁺T cell responses. In this Opinion article, the authors summarize the existing DC-targeting approaches; they discuss whether these vaccines are superior to current vaccines and what future studies should entail to successfully introduce these vaccines into a clinical setting.

Recent evidence indicates that adaptive T cell-mediated immune responses can regulate innate lymphocytes (natural killer cells and innate lymphoid cells) in an interleukin-2-dependent manner. The authors propose a model in which adaptive T cells function as peripheral antigen-specific sensors that recruit and activate innate lymphocytes to amplify and coordinate local immune responses.

Natural killer T (NKT) cell defects have been implicated in several diseases such as autoimmunity, asthma and cancer, but will targeting them really be of clinical benefit? Here, the authors investigate this question and conclude that more careful studies are needed before the true clinical potential of NKT cell-targeted therapies can be determined.

Cells of the mononuclear phagocyte system (MPS) are usually defined by particular functional or phenotypical characteristics. However, this has led to confusion in the field, as many of the criteria that are used to define a particular cell population may actually be shared with other cell types. In this Opinion article, the authors propose that a new nomenclature that is based on cell ontogeny could enable a more robust classification of MPS cells.

Three models have been proposed to explain the link between T cell division and differentiation — epigenetic changes, asymmetric division and the direct regulation of gene expression by cell cycle factors. In support of the third model, this Opinion article describes cell cycle-independent roles for the cyclin-dependent kinases as regulators of immunologically relevant transcription factors.