Imidazoquinoline acts as immune adjuvant for functional alteration of thymic stromal lymphopoietin-mediated allergic T cell response.
Atopic dermatitis is a major allergic disease that develops through dysregulation of Th2-mediated inflammation. Although dendritic cells (DCs) have been thought to play a critical role in the upstream phase of the allergic cascade, conventional drugs such as steroids and chemical mediator antagonists target the effector cells or factors in allergic inflammation. Recently, it has been demonstrated that interaction between thymic stromal lymphopoietin (TSLP) and human DCs plays an essential role in evoking inflammatory Th2 responses in allergy through OX40 ligand expression on DCs. In this study, we provide evidence that R848, an imidazoquinoline compound, which is a TLR ligand and a strong Th1 response-inducing reagent, is a potent adjuvant for the alteration of the Th2-inducing potency of human DCs activated by TSLP (TSLP-DCs). R848 inhibited the inflammatory Th2-inducing capacity of TSLP-DCs and redirected them to possessing an IL-10 and IFN-gamma-producing regulatory Th1-inducing capacity. This functional alteration depended on both repression of OX40 ligand expression and induction of IL-12 production from DCs by the addition of R848. Additionally, R848 had the ability to inhibit the TSLP-mediated expansion and maintenance of the Th2 memory response. These findings suggest that imidazoquinoline may be a useful in the treatment of allergic diseases that are triggered by TSLP.
Torii
Yoshitaro
Y
First Department of Internal Medicine, Kansai Medical University, Osaka, Japan.
Ito
Tomoki
T
Amakawa
Ryuichi
R
Sugimoto
Hiroyuki
H
Amuro
Hideki
H
Tanijiri
Tsutomu
T
Katashiba
Yuichi
Y
Ogata
Makoto
M
Yokoi
Takashi
T
Fukuhara
Shirou
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000276:immunology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D053278:OX40 Ligand / Q000276:immunology; D013256:Steroids / Q000627:therapeutic use; D018418:Th2 Cells / Q000276:immunology*; D000094632:Thymic Stromal Lymphopoietin
D000276:Adjuvants, Immunologic; D016207:Cytokines; C508609:IL10 protein, human; D007093:Imidazoles; D053278:OX40 Ligand; D013256:Steroids; C089251:TNFSF4 protein, human; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; C402365:resiquimod; D000094632:Thymic Stromal Lymphopoietin