Linking Inflammation to Natural Killer T Cell Activation

Nuffield Department of Clinical Medicine, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, United Kingdom.
PLoS Biology (Impact Factor: 9.34). 10/2009; 7(10):e1000226. DOI: 10.1371/journal.pbio.1000226
Source: PubMed


Immune activation is often associated with inflammation, but inflammation's role in the expansion of antigen-specific immune responses remains unclear. This primer focuses on recent findings that show how specific natural killer T cells are activated by inflammatory messengers, thus illuminating the cellular and molecular links between immunity and inflammation.

Download full-text


Available from: Mariolina Salio
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In a related work by the authors, high-order sigma-delta (ΣΔ) modulators with distinct noise transfer function (NTF) zeros are decomposed into second-order and first-order subsystems, whose state-trajectories are then investigated by continuous-time embedding. This paper, based on the properties of these subsystems, furthers the study by introducing a scalable numerical method to locate the fixed-points on the generalized Poincare sections. A closed-form tangent linear manifold matrix for an arbitrary order modulator is derived, enabling the stability determination of the fixed-points and the accompanying limit cycles. Numerical examples show that the estimated DC input bound based on the boundary transition flow assumption cannot be relied on for modulators of order greater than four.
    Full-text · Conference Paper · Feb 2002
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Neutrophils are the main effector cells during inflammation, but they can also control excessive inflammatory responses by secreting anti-inflammatory cytokines. However, the mechanisms that modulate their plasticity remain unclear. We now show that systemic serum amyloid A 1 (SAA-1) controls the plasticity of neutrophil differentiation. SAA-1 not only induced anti-inflammatory interleukin 10 (IL-10)-secreting neutrophils but also promoted the interaction of invariant natural killer T cells (iNKT cells) with those neutrophils, a process that limited their suppressive activity by diminishing the production of IL-10 and enhancing the production of IL-12. Because SAA-1-producing melanomas promoted differentiation of IL-10-secreting neutrophils, harnessing iNKT cells could be useful therapeutically by decreasing the frequency of immunosuppressive neutrophils and restoring tumor-specific immune responses.
    Full-text · Article · Oct 2010 · Nature Immunology
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cardiovascular disease is the largest cause of morbidity and premature mortality and its major underlying pathology is atherosclerosis. Atherosclerosis commences with the deposition of lipids in the artery wall due to trapping by proteoglycans. Trapped lipoproteins are chemically and enzymatically modified to yield pro-inflammatory species that induce adhesion molecule expression on endothelial cells leading to the recruitment of multiple species of immune cells and a chronic inflammatory response. Ongoing remodelling of the vessel and later morphological changes generate "vulnerable" plaques, the acute rupture of which generates the clinical event. The major medical therapies are anti-hypertensives and lipid lowering agents. Although these therapies are amongst the most efficacious in cardiovascular medicine, in optimised well-controlled clinical trials the maximum effect is limited to an approximately 30% reduction in cardiovascular events. Hence, a huge burden of disease remains refractory to current therapies and atherosclerosis and its sequelae persist as a therapeutic target of immense importance. Potential therapeutic targets include the proteoglycan: lipoprotein interaction in the vessel wall, circulating and vessel wall associated atherogenic lipid species and the immune system. Anti-inflammatory therapies include specific cytokine antagonists and cytokine neutralizing antibodies, specific immune cell depleting antibodies and cell therapies using antigen specific regulatory T-cells and regulatory B-cells. In this review, we describe the process of atherosclerosis as it involves the role of chronic inflammation in the development and progression of atherosclerotic plaques and then the manner in which some of these inflammatory processes represent therapeutic targets.
    Full-text · Article · Apr 2011 · Pharmacology [?] Therapeutics
Show more