Lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis

Pineda, M. A. , Al-Riyami, L., Harnett, W. and Harnett, M. M. (2014) Lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis. Clinical and Experimental Immunology, 177(1), pp. 13-23. (doi: 10.1111/cei.12252) (PMID:24666108) (PMCID:PMC4089150)

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Abstract

Parasitic worms are able to survive in their mammalian host for many years due to their ability to manipulate the immune response by secreting immunomodulatory products. It is increasingly clear that, reflecting the anti-inflammatory actions of such worm-derived immunomodulators, there is an inverse correlation between helminth infection and autoimmune diseases in the developing world. As the decrease in helminth infections due to increased sanitation has correlated with an alarming increase in prevalence of such disorders in industrialised countries, this "Hygiene Hypothesis" has led to the proposal that worms and their secreted products offer a novel platform for the development of safe and effective strategies for the treatment of autoimmune disorders. Here we review the anti-inflammatory effects of one such immunomodulator, ES-62 on innate and adaptive immune responses and the mechanisms it exploits to afford protection in the murine Collagen Induced Arthritis (CIA) model of rheumatoid arthritis (RA). As its core mechanism involves targeting of IL-17 responses, which despite being pathogenic in RA are important for combating infection, we discuss how its selective targeting of IL-17 production by Th17 and γδ T cells, whilst leaving that of CD49b+ Natural Killer (NK and NK T) cells intact, reflects the ability of helminths to modulate the immune system without immunocompromising the host. Exploiting helminth immunomodulatory mechanisms therefore offers the potential for safer therapies than current biologics, such as "IL-17 blockers", that are not able to discriminate sources of IL-17 and hence present adverse effects that limit their therapeutic potential.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and Al-Riyami, Dr Lamyaa and Pineda, Dr Miguel
Authors: Pineda, M. A., Al-Riyami, L., Harnett, W., and Harnett, M. M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Clinical and Experimental Immunology
Publisher:Wiley
ISSN:0009-9104
ISSN (Online):1365-2249
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Clinical and Experimental Immunology 177(1):13-23
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
495342ES-62, TLR4, the Mast Cell and development of novel drugs for mast cell-mediated inflammationMargaret HarnettWellcome Trust (WELLCOME)086852/Z/08/ZIII -IMMUNOLOGY
484131Exploiting the host-parasite relationship to develop novel safe anti-inflammatory therapiesMargaret HarnettArthritis Research UK (ARC)MP/18413III -IMMUNOLOGY