The parasitic worm product ES-62 up-regulates IL-22 production by γδ T cells in the murine model of Collagen-Induced Arthritis

Harnett, M. , Harnett, W. and Pineda, M. A. (2014) The parasitic worm product ES-62 up-regulates IL-22 production by γδ T cells in the murine model of Collagen-Induced Arthritis. Inflammation and Cell Signaling, 1(5), e308. (doi: 10.14800/ics.308)

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S-62 is a phosphorylcholine (PC)-containing glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that acts to modulate the host immune response to promote the establishment of chronic helminth infection. Reflecting its anti-inflammatory actions, we have previously reported that ES-62 protects mice from developing Collagen-Induced Arthritis (CIA): thus, as this helminth-derived product may exhibit therapeutic potential in Rheumatoid Arthritis (RA), it is important to understand the protective immunoregulatory mechanisms triggered by ES-62 in this model in vivo. We have established to date that ES-62 acts by downregulating pathogenic Th17/IL-17-mediated responses and upregulating the regulatory cytokine IL-10. In addition, our studies have identified that IL-22, another member of the IL-10 family of cytokines, exerts dual pathogenic and protective roles in this model of RA with ES-62 harnessing the cytokine’s inflammation-resolving and tissue repair properties in the joint during the established phase of disease. Here, we discuss the counter-regulatory roles of IL-22 in the murine model of CIA and present additional novel data showing that ES-62 selectively induces γδ T cells with the capacity to induce IL-22 production and that gd T cells with the capacity to produce IL-22, but not IL-17, induced during CIA can be identified by their expression of TLR4. Moreover, we also show that treatment of mice undergoing CIA with the active PC moiety of ES-62, in the form of PC conjugated to BSA, is not only sufficient to mimic the ES-62-dependent suppression of pathogenic IL-17 responses shown previously but also that of the IL-22 and IL-10 up-regulation observed with the parasitic worm product during CIA. These findings not only reinforce the potential of IL-22, firstly described as a Th17-related pro-inflammatory cytokine, as a protective factor in arthritis but also suggest that drugs based on the PC moiety found in ES-62 may be able to harness the joint-protecting activities of IL-22 therapeutically.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and Pineda, Dr Miguel
Authors: Harnett, M., Harnett, W., and Pineda, M. A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Inflammation and Cell Signaling
Publisher:Smart Science & Technology
Copyright Holders:Copyright © 2014 The Authors
First Published:First published in Inflammation and Cell Signaling 1(5):e308
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