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
U2 - 10.1111/imm.12208
DO - 10.1111/imm.12208
M3 - Article
SN - 0019-2805
VL - 141
SP - 457
EP - 466
JO - Immunology
JF - Immunology
IS - 3
ER -