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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Publisher's URL: http://dx.doi.org/10.14800/ics.308
Abstract
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 |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| 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 |
| ISSN: | 2330-7803 |
| 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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