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

David T. Rodgers, Miguel A. Pineda, Mairi A. McGrath, Lamyaa Al-Riyami, William Harnett, Margaret M. Harnett

Research output: Contribution to journalArticle

30 Citations (Scopus)
62 Downloads (Pure)

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. Towards this, we have established to date that ES-62 protection in CIA is associated with suppressed Th1/Th17 responses, reduced collagen-specific IgG2a antibodies and increased IL-10 production by splenocytes. IL-10-producing regulatory B cells (Bregs) have been proposed to suppress pathogenic Th1/Th17 responses in CIA: interestingly therefore, whilst 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 TLR4 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.
Original languageEnglish
Pages (from-to)457–466
Number of pages10
JournalImmunology
Volume141
Issue number3
Early online date10 Feb 2014
DOIs
Publication statusPublished - Mar 2014

Keywords

  • B cell
  • immunomodulation
  • helminth
  • ES-62
  • interleukin-10-producing B cells
  • parasitic helminths
  • rheumatoid arthritis

Fingerprint Dive into the research topics of 'Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of IL-10-producing B cells and reduced plasma cell infiltration of the joints'. Together they form a unique fingerprint.

  • Cite this