Macrophages – Balancing Tolerance and Immunity

Stoy, Nicholas

doi:10.1002/3527607021.ch10

Cited by 2 publications

(1 citation statement)

References 444 publications

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“…(2008) showing raised levels of several cytokines in both plasma and CSF. Their data are consistent with the view that innate immune cells are autonomously activated either by intrinsic huntingtin‐related abnormalities and/or by alterations in immune responsiveness to toll‐like receptors or other receptor inputs, resulting in a disturbed balance of pro‐ and anti‐inflammatory cytokines in the blood and CSF characteristic of chronic inflammatory conditions (Stoy 2005a,b; Bunt et al. 2009).…”

Section: Discussionsupporting

confidence: 85%

Blood levels of kynurenines, interleukin‐23 and soluble human leucocyte antigen‐G at different stages of Huntington’s disease

Forrest

Mackay

Stoy

et al. 2009

Journal of Neurochemistry

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There is substantial evidence that abnormal concentrations of oxidised tryptophan metabolites, produced via the kynurenine pathway, contribute to progressive neurodegeneration in Huntington's disease. We have now examined the blood levels of these metabolites in patients at different stages of Huntington's disease, assessed both in terms of clinical disease severity and numbers of CAG repeats. Close relatives of the patients were included in the study as well as unrelated healthy controls. Levels of lipid peroxidation products, the proinflammatory cytokine interleukin (IL)-23 and the soluble human leucocyte antigen-G (sHLA-G) were also measured. There were lower levels of tryptophan and a higher kynurenine : tryptophan ratio, indicating activation of indoleamine-2,3-dioxygenase, in the most severely affected group of patients, with increased levels of IL-23 and sHLA-G. Marked correlations were noted between IL-23 and the patient severity group, anthranilic acid levels and the number of CAG repeats, and between anthranilic acid and IL-23, supporting our previous evidence of a relationship between anthranilic acid and inflammatory status. Tryptophan was negatively correlated with symptom severity and number of CAG repeats, and positively correlated with sHLA-G. The results support the proposal that tryptophan metabolism along the kynurenine pathway in Huntington's disease is related to the degree of genetic abnormality, to clinical disease severity and to aspects of immunopathogenesis.

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Section: Discussionsupporting

confidence: 85%

Blood levels of kynurenines, interleukin‐23 and soluble human leucocyte antigen‐G at different stages of Huntington’s disease

Forrest

Mackay

Stoy

et al. 2009

Journal of Neurochemistry

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Innate origins of multiple sclerosis pathogenesis: Implications for computer‐assisted design of disease‐modifying therapies

Stoy

2011

Drug Development Research

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The rational development of disease-modifying therapies for multiple sclerosis (MS) requires a detailed knowledge of disease pathogenesis, but this remains incomplete. Dynamic computerassisted modeling of MS is currently hindered by uncertainties about the connectivity, compartmentalization, and dynamic sequencing of the components of the disease process. The present work presents a simple but versatile model of the mammalian immune system, incorporating both innate and adaptive immunity and innate and adaptive tolerance. The model is applied to MS and its animal model, experimental autoimmune encephalomyelitis (EAE), to interrogate the concept of initiation of MS lesions through activation of the peripheral innate immune system, triggering auto-reactive T cells against myelin antigens in the central nervous system (CNS). The model also addresses the modulation of proinflammatory neurotoxic responses by the generation of regulatory T cells (adaptive tolerance) and clarifies the role of innate tolerance, a part of the immune system that has been little explored in MS to date. Some ramifications of the model are mentioned, including its relevance to existing disease-modifying therapies and the need to look more closely at the innate immune system for future therapeutic targets. Drug Dev Res 72:674-688,

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Macrophages – Balancing Tolerance and Immunity

Cited by 2 publications

References 444 publications

Blood levels of kynurenines, interleukin‐23 and soluble human leucocyte antigen‐G at different stages of Huntington’s disease

Blood levels of kynurenines, interleukin‐23 and soluble human leucocyte antigen‐G at different stages of Huntington’s disease

Innate origins of multiple sclerosis pathogenesis: Implications for computer‐assisted design of disease‐modifying therapies

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