Imiquimod promotes Th1 and Th17 responses via NF‑&kappa;B‑driven IL‑12 and IL‑6 production in an <em>in vitro</em> co‑culture model

Cho,Yerim; Kwon,Jiho; Kim,Tae Sung

doi:10.3892/etm.2025.12925

Imiquimod promotes Th1 and Th17 responses via NF‑κB‑driven IL‑12 and IL‑6 production in an in vitro co‑culture model

Authors:
- Yerim Cho
- Jiho Kwon
- Tae Sung Kim
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Affiliations: Department of Life Sciences, College of Life Science and Biotechnology, Korea University, Seoul 02841, Republic of Korea
Published online on: July 21, 2025 https://doi.org/10.3892/etm.2025.12925
Article Number: 175

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Abstract

Although imiquimod (IMQ) is widely used to induce psoriasis‑like inflammation in mouse models, its direct effects on dendritic cells (DCs) and their capacity to drive T cell polarization remain poorly defined. The systemic complexity of in vivo models hinders the ability to delineate the direct, cell‑intrinsic effects of IMQ. To address this gap, an in vitro DC‑CD4⁺ T cell co‑culture system was established using bone marrow‑derived DCs and naïve CD4⁺ T cells isolated from OT‑II mice, enabling precise evaluation of the direct immunomodulatory effects of IMQ. IMQ treatment markedly upregulated maturation markers (CD40, CD80, CD86 and major histocompatibility complex class II), and increased IL‑12 and IL‑6 secretion in a dose‑dependent manner. These effects were significantly attenuated by NF‑κB inhibitors (caffeic acid phenethyl ester and Bay 11‑7082), indicating a critical role for NF‑κB signaling in DC activation. When co‑cultured with naïve CD4⁺ T cells, IMQ‑treated DCs promoted robust differentiation toward T helper (Th)1 and Th17 subsets. Neutralization of IL‑12 and IL‑6 in the co‑culture system significantly reduced the frequencies of Th1 and Th17 cells and their cytokine output, confirming that these responses were mediated by DC‑derived cytokines. Collectively, the present findings demonstrated that IMQ directly activated DCs via NF‑κB signaling and induced pathogenic Th cell responses through IL‑12 and IL‑6 production. By eliminating confounding in vivo factors, the present study provided evidence for the DC‑intrinsic effects of IMQ and offered mechanistic insights into the cellular pathways linking innate immune sensing to adaptive T cell responses in psoriasis.

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