Enhanced TARC production by dust-mite allergens and its modulation by immunosuppressive drugs in PBMCs from patients with atopic dermatitis

Hitoshi Akiba,Fumio Kaneko,Koichiro Nakamura,Akiko Nishibu,Hirotoshi Furukawa,Kunihiko Tamaki,Hidehisa Saeki,Noritaka Oyama,Xuyei Zheng,Michiko Tojo,Yuichiro Tsunemi

doi:10.1016/j.jdermsci.2004.02.008

Abstract

Background : Thymus and activation regulated chemokine (TARC) is a CC chemokine that attracts CCR4 + T cells. We reported previously that TARC is an important chemokine that defines Th2 imbalance in the pathogenesis of atopic dermatitis (AD). Objectives : This study was undertaken to clarify TARC producing cells in peripheral blood mononuclear cells (PBMCs), the regulation of dust mite-allergen clude extract (DME) and different immunosuppressive drugs (Tacrolimus (FK506), cyclosporine (CsA), dexamethasone (Dex)) on TARC production by peripheral PBMCs from AD patients in vitro. Methods : Monocyte derived dendritic cells (MoDCs) were generated from and TARC mRNA levels were examined and comapared with those from T cells in PBMCs from AD patients. PBMCs were cultured with or without DME and/or immunosuppressive drugs (Tacrolimus, CsA, Dex) for 7 days and TARC levels were measured. Results : PBMCs from AD patients which were cultured with DME stimulation for 7 days showed significantly higher levels of TARC production than those from healthy controls. RT–PCR demonstrated that TARC mRNA was expressed in CD4 + T cells, CD8 + T cells and MoDCs. Tacrolimus, CsA and Dex individually suppressed TARC production by PBMCs from AD patients which were co-cultured with DME for 7 days. Gel shift analysis revealed differential inhibitory effects of these immunosuppressive drugs on NFκB activity in PBMCs from AD patients. Conclusion : Our data demonstrate that TARC producing cells are MoDCs, T cells as well as epidermal keratinocytes in AD. We suggest that MoDCs might regulate the immune responses by attracting T cells and CD25 + T cells in the pathogenesis of AD. We also showed the important role of DME on TARC production and the inhibitory effect of the immunosuppressive drugs on TARC production by PBMCs from AD patients, that can regulate ongoing immune responses in the pathogenesis of AD.

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