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Mehran Goreishi, MD, University of British Columbia, Vancouver, BC. Systemic lupus erythematosus (SLE) is a chronic relapsing remitting autoimmune disease. Various environmental factors in addition to genetic susceptibility have been proposed to be crucial for the initiation and exacerbation of autoimmunity in SLE. UV light is an important environmental factor in this regard. UV-induced skin cell damage results in release of nuclear protein antigens. Antibodies against these antigens result in immune complex formation and tissue destruction. Evidence suggests that viral infections also result in flares of disease through production of interferon alpha. In this study we will use the combination of ultraviolet light B (UVB) and the topical cream imiquimod which activates immune cells by induction of interferon alpha to induce lupus autoimmunity in mice. We will study the mechanisms of synergistic effects of these two factors in disease induction and promotion. This may lead to the development of new therapies for the treatment and prevention of SLE. Peer Reviewed Publications Supported by the CDF (2002-2007): 1: Najar HM, Dutz JP. Topical TLR9 agonists induce more efficient cross-presentation of injected protein antigen than parenteral TLR9 agonists do. Eur J Immunol. 2007 Aug;37(8):2242-56. PMID: 17634951 [pubMed - indexed for MEDLINE] This was funded in part by my 2006 and 2007 CDF grants 2: Ghoreishi M, Dutz JP. Tolerance induction by transcutaneous immunization through ultraviolet-irradiated skin is transferable through CD4+CD25+ T regulatory cells and is dependent on host-derived IL-10. J Immunol. 2006 Feb 15;176(4):2635-44. PMID: 16456026 [PubMed - indexed for MEDLINE] This was funded in part by my 2005 CDF grant. 3: Schutze-Redelmeier MP, Kong S, Bally MB, Dutz JP. Antennapedia transduction sequence promotes anti tumor immunity to epicutaneously administered CTL epitopes. Vaccine. 2004 May 7;22(15-16):1985-91. PMID: 15121311 [PubMed - indexed for MEDLINE] 4: Klimuk SK, Najar HM, Semple SC, Aslanian S, Dutz JP. Epicutaneous application of CpG oligodeoxynucleotides with peptide or protein antigen promotes the generation of CTL. J Invest Dermatol. 2004 Apr;122(4):1042-9. PMID: 15102096 [PubMed - indexed for MEDLINE] 5: Kahlon R, Dutz JP. Skin immune responses to peptide and protein antigen are TLR4 independent. Cell Immunol. 2003 Dec; 226(2):116-23. PMID: 14962499 [PubMed - indexed for MEDLINE] 6: Kahlon R, Hu Y, Orteu CH, Kifayet A, Trudeau JD, Tan R, Dutz JP. Optimization of epicutaneous immunization for the induction of CTL. Vaccine. 2003 Jun 20;21(21-22):2890-9. PMID: 12798632 [PubMed - indexed for MEDLINE] Publications # 3-6 were funded in part by my 2002 CDF grant. ©2008 |
