TY  - JOUR
AV  - public
A1  - Strid, J
A1  - Tan, LA
A1  - Strobel, S
A1  - Londei, M
A1  - Callard, R
Y1  - 2007/04/18/
UR  - http://dx.doi.org/10.1371/journal.pone.0000387
JF  - PLoS One
SN  - 1932-6203
VL  - 2
IS  - 4
KW  - Animals
KW  -  Antibodies
KW  -  Arthritis
KW  -  Experimental
KW  -  Cell Proliferation
KW  -  Collagen Type II
KW  -  Disease Progression
KW  -  Interferon-gamma
KW  -  Mice
KW  -  Mice
KW  -  Inbred DBA
KW  -  Skin
KW  -  T-Lymphocytes
ID  - discovery69315
TI  - Epicutaneous immunization with type II collagen inhibits both onset and progression of chronic collagen-induced arthritis.
N1  - © 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.
N2  - 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.
ER  -