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.
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.
Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
David T
DT
Rodgers
Miguel A
MA
Pineda
Mairi A
MA
McGrath
Lamyaa
L
Al-Riyami
William
W
Harnett
Margaret M
MM
Harnett
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D018501:Antirheumatic Agents / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000097:blood / Q000139:chemically induced / Q000276:immunology / Q000517:prevention & control*; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D003094:Collagen / Q000276:immunology; D015801:Helminth Proteins / Q000494:pharmacology*; D016753:Interleukin-10 / Q000378:metabolism*; D007596:Joints / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000906:Antibodies; D015703:Antigens, CD; D018501:Antirheumatic Agents; D015415:Biomarkers; C435884:ES-62 protein, Acanthocheilonema viteae; D015801:Helminth Proteins; C556062:IL10 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D016753:Interleukin-10; D003094:Collagen
ES-62; interleukin-10-producing B cells; parasitic helminths; rheumatoid arthritis