Strid, J;
Tan, LA;
Strobel, S;
Londei, M;
Callard, R;
(2007)
Epicutaneous immunization with type II collagen inhibits both onset and progression of chronic collagen-induced arthritis.
PLoS One
, 2
(4)
, Article e387. 10.1371/journal.pone.0000387.
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Abstract
Epicutaneous immunization is a potential non-invasive technique for antigen-specific immune-modulation. Topical application of protein antigens to barrier-disrupted skin induces potent antigen-specific immunity with a strong Th2-bias. In this study, we investigate whether the autoimmune inflammatory response of chronic collagen-induced arthritis (CCIA) in DBA/1-TCR-beta Tg mice can be modified by epicutaneous immunization. We show that epicutaneous immunization with type II collagen (CII) inhibited development and progression of CCIA and, importantly, also ameliorated ongoing disease as indicated by clinical scores of disease severity, paw swelling and joints histology. Treated mice show reduced CII-driven T cell proliferation and IFN-gamma production, as well as significantly lower levels of CII-specific IgG2a serum antibodies. In contrast, CII-driven IL-4 production and IgE antibody levels were increased consistent with skewing of the CII response from Th1 to Th2 in treated mice. IL-4 production in treated mice was inversely correlated with disease severity. Moreover, T cells from treated mice inhibited proliferation and IFN-gamma production by T cells from CCIA mice, suggesting induction of regulatory T cells that actively inhibit effector responses in arthritic mice. The levels of CD4(+)CD25(+) T cells were however not increased following epicutaneous CII treatment. Together, these results suggest that epicutaneous immunization may be used as an immune-modulating procedure to actively re-programme pathogenic Th1 responses, and could have potential as a novel specific and simple treatment for chronic autoimmune inflammatory diseases such as rheumatoid arthritis.
| Type: | Article |
|---|---|
| Title: | Epicutaneous immunization with type II collagen inhibits both onset and progression of chronic collagen-induced arthritis. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0000387 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0000387 |
| Language: | English |
| Additional information: | © 2007 Strid et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. PMCID: PMC1849892 Research at the Institute of Child Health and Great Ormond Street Hospital for Children National Health Service (NHS) Trust benefits from research and development funding received from the UK NHS Executive. This work was additionally funded by the Arthritis Research Campaign (ARC) UK. Nothing to disclose. |
| Keywords: | Animals, Antibodies, Arthritis, Experimental, Cell Proliferation, Collagen Type II, Disease Progression, Interferon-gamma, Mice, Mice, Inbred DBA, Skin, T-Lymphocytes |
| UCL classification: | UCL |
| URI: | https://discovery.ucl.ac.uk/id/eprint/69315 |
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