Opinion

In this Opinion article, Caroline Jefferies and colleagues discuss the evidence in support of a role for TRIM proteins in autoimmune and autoinflammatory disease through their ability to regulate the inflammasome and pro-inflammatory cytokine and interferon production.

Erica Herzog and colleagues put forward the opinion that fibrocytes, a little-studied population of monocyte-derived cells that have properties of both macrophages and fibroblasts, have unique roles in chronic inflammation that warrant further study.

Despite the frequently proposed 'redundancy' of the chemokine system, these authors put forward the opinion that targeting a single chemokine receptor can be effective in treating inflammatory disease provided that thein vivopotency is sufficient.

This article describes the molecular mechanisms involved in T cell senescence and T cell exhaustion, and proposes that these states are controlled by distinct molecular pathways. Blocking exhaustion rather than senescence may be a safer way to enhance immunity to persistent infections and in ageing.

In this Opinion article, David Finlay and Doreen Cantrell explore the molecular pathways that may link CD8⁺ T cell metabolism with effector versus memory CD8⁺T cell differentiation through the control of T cell migration.

The lack of natural immunity against HIV has been a major hindrance to the search for immune correlates of protection. Here, the authors propose a new approach for clinical trials of HIV vaccine efficacy that should help to increase our chances of identifying immune correlates of protection.

This Perspective article describes the ways in which the intestinal microbiota can interact with the host immune system to promote both pro- and anti-inflammatory immune responses. The authors discuss the important implications of this for not only intestinal, but also for systemic inflammatory diseases.

This Opinion article describes the newly discovered conserved immunological and structural features of the sequence-variable regions of HIV-1 gp120, which the authors suggest warrant the reappraisal of these regions as vaccine targets.

This article outlines how helminth-derived immunomodulators can subvert pro-inflammatory responses by using host innate immune receptors to trigger divergent signalling pathways in antigen-presenting cells and proposes that these immunomodulators can be used as tools to dissect the pathways required to promote anti-inflammatory responses.

Invariant natural killer T (iNKT) cells are thought to be autoreactive by 'design'. Here, Laurent Gapin describes how iNKT cell autoreactivity might be triggered and proposes that several self lipids are probably involved in the positive selection of iNKT cells and the autoreactivity of these cells in peripheral tissues.

Haematopoietic stem cells (HSCs) can reside as dormant cells in endosteal niches in the bone marrow, where they are resistant to certain types of chemotherapy. In this article, the authors suggest that by first awakening dormant HSCs to become actively self-renewing cells, this resistance to chemotherapy could be overcome.

This Opinion article discusses the evidence for and the limitations of the three main models of inflammasome activation. The authors propose that the production of reactive oxygen species might be a common factor downstream of many types of inflammasome activator.

In this Opinion article, the authors suggest that more extensive use of laboratory measurements could help to expedite clinical trials of immunotherapy. They propose that surrogate end points could be used in place of clinical end points to determine drug safety, disease progression and therapeutic efficacy.

In this Opinion article, the authors discuss our current understanding of the roles of immunoproteasomes and thymoproteasomes in T cell receptor repertoire formation and propose that immunoproteasomes have additional roles in cytokine production and T helper cell differentiation.

These authors propose that the T helper 17 cell and induced regulatory T cell lineages were the first T cells of the adaptive immune system to evolve in vertebrates as a means to counter-regulate immune responses in the gut to foster a large, diverse commensal microbiota for the benefit of the host.

Here, Michael Cancro proposes a model to explain how B cell fate is determined by balancing signals that select B cells of suitable reactivity with signals that support survival. This balance is said to be mediated by crosstalk between the mediators downstream of the B cell receptor (BCR) and receptor for B cell-activating factor (BAFFR).

In this Opinion article, Betty Diamond and colleagues propose that common serum antibodies that crossreact with brain antigens might be responsible for many acquired changes or congenital impairments in cognition and behaviour in the absence of overt brain inflammation.

Recent studies indicate that haematopoietic progenitor cells have more plasticity with regard to lineage choice than previously appreciated. To account for this developmental plasticity, Rhodri Ceredig and colleagues propose a new model of haematopoiesis.

How the T-cell receptor translates ligand affinity to an appropriate cellular response has puzzled immunologists for decades. In this Opinion article, the authors propose a new model to explain this, which is based on the duration of receptor–ligand binding and on a 'zipper' mechanism that mediates receptor–co-receptor interactions.

Here, Harvey Cantor and Mari Shinohara propose that the secreted and intracellular isoforms of osteopontin differentially regulate the development of distinct T-helper-cell subsets and, consequently, adaptive immune responses to foreign and self antigens.