Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints

Rodgers, D.T., Pineda, M.A. , McGrath, M.A., Al-Riyami, L., Harnett, W. and Harnett, M.M. (2014) Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints. Immunology, 141(3), pp. 457-466. (doi: 10.1111/imm.12208) (PMID:24708419) (PMCID:PMC3930382)

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Abstract

We have previously reported that ES-62, a molecule secreted by the parasitic filarial nematode Acanthocheilonema viteae, protects mice from developing collagen-induced arthritis (CIA). Together with increasing evidence that worm infection may protect against autoimmune conditions, this raises the possibility that ES-62 may have therapeutic potential in rheumatoid arthritis and hence, it is important to fully understand its mechanism of action. To this end, we have established to date that ES-62 protection in CIA is associated with suppressed T helper type 1 (Th1)/Th17 responses, reduced collagen-specific IgG2a antibodies and increased interleukin-10 (IL-10) production by splenocytes. IL-10-producing regulatory B cells have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, although the levels of IL-10-producing B cells were decreased in the spleens of mice with CIA, ES-62 was found to restore these to the levels found in naive mice. In addition, exposure to ES-62 decreased effector B-cell, particularly plasma cell, infiltration of the joints, and such infiltrating B cells showed dramatically reduced levels of Toll-like receptor 4 and the activation markers, CD80 and CD86. Collectively, this induction of hyporesponsiveness of effector B-cell responses, in the context of the resetting of the levels of IL-10-producing B cells, is suggestive of a modulation of the balance between effector and regulatory B-cell responses that may contribute to ES-62-mediated suppression of CIA-associated inflammation and inhibition of production of pathogenic collagen-specific IgG2a antibodies.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and McGrath, Miss Mairi and Al-Riyami, Dr Lamyaa and Pineda, Dr Miguel
Authors: Rodgers, D.T., Pineda, M.A., McGrath, 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:Immunology
Publisher:Blackwell
ISSN:0019-2805
ISSN (Online):1365-2567
Copyright Holders:Copyright © 2013 The Authors
First Published:First published in Immunology 141(3):457-466
Publisher Policy:Reproduced under a Creative Commons License
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
484131Exploiting the host-parasite relationship to develop novel safe anti-inflammatory therapiesMargaret HarnettArthritis Research UK (ARC)MP/18413III -IMMUNOLOGY