Minocycline promotes the generation of dendritic cells with regulatory properties

Abstract

Abstract Minocycline, which has long been used as a broad-spectrum antibiotic, also exhibits non-antibiotic properties such as inhibition of inflammation and angiogenesis. In this study, we show that minocycline significantly enhances the generation of dendritic cells (DCs) from mouse (BM) cells when used together with GM-CSF and IL-4. DCs generated from BM cells in the presence of minocycline (Mino-DCs) demonstrate the characteristics of regulatory DCs. Compared with control DCs, Mino-DCs are resistant to subsequent maturation stimuli, impaired in MHC class II-restricted exogenous Ag presentation, and show decreased cytokine secretion and allogeneic T cell stimulation in vitro. Mino-DCs also have a decreased ability to prime alloantigen-specific T cells when transferred to allogeneic mice. Splenic Mino-DCs generated in mice by injecting minocycline together with GM-CSF are also severely impaired in priming alloantigen-specific T cells in allogeneic mice. In allogeneic mice, Mino-DCs induce expansion of CD4+CD25+Foxp3+ T regulatory cells. Our study identifies minocycline as a new pharmacological agent that could be potentially used to increase the production of regulatory DCs for cell therapy to treat autoimmune disorders, allergy, and transplant rejection.