Topical application of siRNA targeting cutaneous dendritic cells in allergic skin disease.
RNA interference is a promising method for silencing specific genes and has great potential for therapeutic applications. However, the major hurdle for therapeutic application is the limited stability of double-strand RNA (dsRNA) and the absence of a reliable delivery method to target cells. Skin appears to be a favorable target for small interfering RNA (siRNA) therapy. Dendritic cells (DCs) exist in the skin and mucosae on the front lines of defense; these cells capture antigens and play a crucial role in inducing immunity and tolerance.In our recent work, we have shown a successful treatment using CD86 siRNA targeting cutaneous DCs. A costimulatory molecule, CD86, is induced on DCs in situ after antigen uptake, and CD86-expressing DCs migrate to the regional lymph nodes to present antigens to T cells. Topical application of cream-emulsified CD86 siRNA ameliorated the clinical manifestations in murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Our method may be advantageous for the treatment of allergic skin diseases.
Azuma
Miyuki
M
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
Ritprajak
Patcharee
P
Hashiguchi
Masaaki
M
D000287:Administration, Topical; D000818:Animals; D051940:B7-2 Antigen / Q000276:immunology; D005260:Female; D006967:Hypersensitivity / Q000235:genetics* / Q000276:immunology / Q000628:therapy*; D007801:Langerhans Cells / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage*
D051940:B7-2 Antigen; D034741:RNA, Small Interfering