PMID- 18461054 OWN - NLM STAT- MEDLINE DCOM- 20080804 LR - 20171116 IS - 1525-0024 (Electronic) IS - 1525-0016 (Linking) VI - 16 IP - 7 DP - 2008 Jul TI - Topical application of cream-emulsified CD86 siRNA ameliorates allergic skin disease by targeting cutaneous dendritic cells. PG - 1323-30 LID - 10.1038/mt.2008.91 [doi] AB - Induction of the co-stimulatory molecule CD86 on dendritic cells (DCs) in the peripheral tissues is a critical event in triggering antigen-specific immune responses. In this study, we propose a new small interfering RNA (siRNA)-based therapy using cream-emulsified CD86 siRNA, targeting DCs for murine contact hypersensitivity (CH) and atopic dermatitis (AD)-like disease. Topical application of CD86 siRNA efficiently inhibited CH and markedly decreased the numbers of infiltrating CD86(+) or major histocompatibility complex (MHC) class II(+) cells in murine ear skin. The total number of cells, the percentage of hapten-carrying DCs, and their CD86 expression in the regional lymph nodes (RLNs) also significantly decreased. These results suggest that the silencing of CD86 in local DCs inhibits the recruitment and migration of DCs into the skin and RLNs, respectively, resulting in reduced antigen-specific local inflammation. The therapeutic efficacy of the CD86 siRNA was confirmed in AD-prone NC/Nga mice. Treatment produced marked amelioration in the clinical manifestations of AD and reduced the antigen-specific production of interleukin-4 (IL-4) and serum immunoglobulin E (IgE) and IgG1. Our results suggest that the targeting of cutaneous DCs by CD86 siRNA may be a promising strategy in the treatment of allergic skin disease. FAU - Ritprajak, Patcharee AU - Ritprajak P AD - Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. FAU - Hashiguchi, Masaaki AU - Hashiguchi M FAU - Azuma, Miyuki AU - Azuma M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20080506 PL - United States TA - Mol Ther JT - Molecular therapy : the journal of the American Society of Gene Therapy JID - 100890581 RN - 0 (B7-2 Antigen) RN - 0 (Emulsions) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (RNA, Small Interfering) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Animals MH - B7-2 Antigen/*genetics/metabolism MH - Base Sequence MH - Cell Movement/drug effects MH - Dermatitis, Allergic Contact/*drug therapy MH - Emulsions MH - Female MH - Gene Silencing MH - Histocompatibility Antigens Class II/analysis MH - Immunoglobulin E/blood MH - Langerhans Cells/*drug effects/metabolism MH - Mice MH - Mice, Inbred BALB C MH - RNA, Small Interfering/*administration & dosage MH - Skin/*drug effects/metabolism EDAT- 2008/05/08 09:00 MHDA- 2008/08/05 09:00 CRDT- 2008/05/08 09:00 PHST- 2008/05/08 09:00 [pubmed] PHST- 2008/08/05 09:00 [medline] PHST- 2008/05/08 09:00 [entrez] AID - S1525-0016(16)32474-1 [pii] AID - 10.1038/mt.2008.91 [doi] PST - ppublish SO - Mol Ther. 2008 Jul;16(7):1323-30. doi: 10.1038/mt.2008.91. Epub 2008 May 6.