Diarylheptanoid from rhizomes of Curcuma kwangsiensis (DCK) inhibited imiquimod-induced dendritic cells activation and Th1/Th17 differentiation

Dendritic cells (DCs) are critical for initiating the activation and differentiation of T cells in inflammatory diseases including psoriasis. Curcuma kwangsiensis S.G. Lee & C.F. Liang is a herb for treating psoriasis and we previously found Diarylheptanoid from rhizomes of Curcuma kwangsiensis (DCK) inhibited keratinocytes proliferation. However, it is unknown whether DCK influences DC functions. Thus we aimed to explore whether DCK affect the major immunological functions of DCs. Primary DCs derived from mouse bone marrow cells and spleen were used for examining their general immunological functions, and OVA-specific T cells from OT-II mice were used for examining the DC-mediated T-helper (Th) 1 and Th17 cells differentiation and effect. We demonstrated DCK suppressed DC uptake of FITC-labeled ovalbumin (OVA) and DC maturation characterized by decreased MHCII, CD80 and CD86 following imiquimod (IMQ) stimulation. DCK also reduced DC expression of the lymphoid-homing chemokine receptor CCR7, and DC migration towards CCL21, the ligand for CCR7. Importantly, DCK significantly reduced the production of proinflammatory cytokines including IL-12, IL-6 and IL-1β by IMQ-stimulated DCs. Moreover, in the coculture of OVA323–339 peptide-pulsed DCs and OVA-specific T cells from OT-II mice, DCK significantly inhibited T cell proliferation and the differentiation of Th1 and Th17 cells. Furthermore, DCK treatment greatly reduced phosphorylation of p65-associated cell signaling pathway in IMQ-stimulated DCs. These data together demonstrate a potential role of DCK in suppressing the biological function of DCs, and provide a possible mechanism for understanding the effects of herb Curcuma kwangsiensis in treating psoriasis. Easy-understanding summary: A novel compound isolated from herbal medicine (DCK) suppressed the biological functions of dendritic cells (DC), including DC activation and DC-mediated Th1 and Th17 cell differentiation, which was associated with the NF-κB signaling pathway. This work suggested a potential therapeutic role of DCK in treating inflammatory skin diseases like psoriasis. [Display omitted] •Diarylheptanoid from rhizomes of Curcuma Kwangsiensis (DCK) is novel compound isolated from a herbal medicine•DCK suppressed imiquimod-activated biological functions of DC•DCK inhibited Th1 and Th17 differentiation by impairing the NF-κB-mediated cytokines production from DC•This work suggested a potential therapeutic role of DCK in treating inflammatory skin