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The Journal of Immunology, 2009, 182, 3556 -3565
Copyright © 2009 by The American Association of Immunologists, Inc.
doi:10.4049/jimmunol.0802972

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Antigen-Specific Suppression of Inflammatory Arthritis Using Liposomes1

Christelle Capini*, Montree Jaturanpinyo2,{dagger}, Hsin-I Chang{dagger}, Srinivas Mutalik{dagger}, Alice McNally*, Shayna Street*, Raymond Steptoe*, Brendan O'Sullivan*, Nigel Davies{dagger} and Ranjeny Thomas3,*

* Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia; and {dagger} School of Pharmacy, University of Queensland, Brisbane, Australia

Existing therapies for rheumatoid arthritis and other autoimmune diseases are not Ag specific, which increases the likelihood of systemic toxicity. We show that egg phosphatidylcholine liposomes loaded with Ag (OVA or methylated BSA) and a lipophilic NF-{kappa}B inhibitor (curcumin, quercetin, or Bay11-7082) suppress preexisting immune responses in an Ag-specific manner. We injected loaded liposomes into mice primed with Ag or into mice suffering from Ag-induced inflammatory arthritis. The liposomes targeted APCs in situ, suppressing the cells’ responsiveness to NF-{kappa}B and inducing Ag-specific FoxP3+ regulatory T cells. This regulatory mechanism suppressed effector T cell responses and the clinical signs of full-blown Ag-induced arthritis. Thus, liposomes encapsulate Ags and NF-{kappa}B inhibitors stably and efficiently and could be readily adapted to deliver Ags and inhibitors for Ag-specific suppression of other autoimmune and allergic diseases.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by Grants 351439 and 508927 from the National Health and Medical Research Council and by the Princess Alexandra Hospital Foundation. R.T. is supported by Arthritis Queensland, B.O.S. and C.C. by Queensland Government Smart State Fellowships, and S.S. by a National Health and Research Council Career Development Award.

2 Current address: Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand.

3 Address correspondence and reprint requests to Prof. Ranjeny Thomas, Diamantina Institute for Cancer, Immunology and Metabolic Medicine, University of Queensland, Princess Alexandra Hospital, Brisbane, Queensland, 4102, Australia. E-mail address: Ranjeny.Thomas{at}uq.edu.au

4 Abbreviations used in this paper: RA, rheumatoid arthritis; AIA, Ag-induced inflammatory arthritis; DiI, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate; EPC, egg phosphatidylcholine; LN, lymph node; DC, dendritic cell; Treg, regulatory T; mBSA, methylated BSA; DiR, 1,1'-dioctadecyl-3,3,3',3'-tetramethylindotricarbocyanine iodide.







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