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

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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. 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

Fingerprint

Experimental Arthritis
Helminths
Plasma Cells
Interleukin-10
B-Lymphocyte Subsets
B-Lymphocytes
Joints
Regulatory B-Lymphocytes
Acanthocheilonema
Collagen
Antibodies
Rheumatoid Arthritis
Spleen
Inflammation
Infection

Keywords

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

Cite this

Rodgers, David T. ; Pineda, Miguel A. ; McGrath, Mairi A. ; Al-Riyami, Lamyaa ; Harnett, William ; Harnett, Margaret M. / 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. In: Immunology. 2014 ; Vol. 141, No. 3. pp. 457–466.
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title = "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",
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.",
keywords = "B cell, immunomodulation, helminth, ES-62, interleukin-10-producing B cells, parasitic helminths , rheumatoid arthritis",
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Rodgers, DT, Pineda, MA, McGrath, MA, Al-Riyami, L, Harnett, W & Harnett, MM 2014, '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', Immunology, vol. 141, no. 3, pp. 457–466. https://doi.org/10.1111/imm.12208

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

In: Immunology, Vol. 141, No. 3, 03.2014, p. 457–466.

Research output: Contribution to journal › Article

TY - JOUR

T1 - 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

AU - Rodgers, David T.

AU - Pineda, Miguel A.

AU - McGrath, Mairi A.

AU - Al-Riyami, Lamyaa

AU - Harnett, William

AU - Harnett, Margaret M.

PY - 2014/3

Y1 - 2014/3

N2 - 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.

AB - 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.

KW - B cell

KW - immunomodulation

KW - helminth

KW - ES-62

KW - interleukin-10-producing B cells

KW - parasitic helminths

KW - rheumatoid arthritis

UR - http://onlinelibrary.wiley.com/journal/10.1111/%28ISSN%291365-2567

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DO - 10.1111/imm.12208

M3 - Article

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EP - 466

JO - Immunology

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SN - 0019-2805

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Rodgers DT, Pineda MA, McGrath MA, Al-Riyami L, Harnett W, Harnett MM. 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. Immunology. 2014 Mar;141(3):457–466. https://doi.org/10.1111/imm.12208

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