Topical application of cream-emulsified CD86 siRNA ameliorates allergic skin disease by targeting cutaneous dendritic cells.
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.
Ritprajak
Patcharee
P
Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan.
Hashiguchi
Masaaki
M
Azuma
Miyuki
M
D000818:Animals; D051940:B7-2 Antigen / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy*; D004655:Emulsions; D005260:Female; D020868:Gene Silencing; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007073:Immunoglobulin E / Q000097:blood; D007801:Langerhans Cells / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012867:Skin / Q000187:drug effects* / Q000378:metabolism
D051940:B7-2 Antigen; D004655:Emulsions; D000949:Histocompatibility Antigens Class II; D034741:RNA, Small Interfering; D007073:Immunoglobulin E