COLCHICINE PROMOTES ANTIGEN CROSS-PRESENTATION BY MURINE DENDRITIC CELLS.

This study by researchers at the University of Texas Southwestern Medical Center demonstrated that MatTek’s Human Langerhans/Dendritic Cells are an excellent in vitro model for investigating and predicting the likely interactions of drugs (Colchicine) with human dendritic cells. Colchicine (COL) is a microtubule depolymerizing drug that has been widely used for the treatment of many inflammatory skin diseases, such as Behc¸et disease, psoriasis, palmoplantar pustulosis, Sweet’s syndrome, and leukocytoclastic vasculitis. With regard to its pharmacological mechanisms of action, COL is thought to primarily inhibit various functions of polymorphonuclear neutrophils, including mitosis, adhesion, migration, and phagocytosis. We recently reported totally unexpected pharmacological activities of COL. Briefly, COL at relatively low concentrations triggered phenotypic maturation of murine bone marrow (BM)-derived dendritic cells (DCs) as well as their production of several cytokines and chemokines. Moreover, BM-DCs pretreated with COL exhibited enhanced capacities to activate allogeneic T cells and to present a foreign protein antigen to immunologically naive CD4 T cells. Interestingly, COL pretreatment markedly improved the ability of BM-DCs to uptake FITC conjugated dextran (DX). Upon local injection in low doses, COL promoted in situ maturation and mobilization of epidermal Langerhans cells and boosted both humoral and cellular immune responses in mice. These observations may appear to be rather contradictory to the conventional view that COL acts as an anti-inflammatory agent (when administered systemically at high doses). Thus, we first sought to study in vitro effects of COL on human DCs. For this purpose, we employed human DC preparations generated from CD34+ progenitors in the cord blood (MatTek Corp., Ashland, MA). To recapitulate the essence of our new observations, COL was found to promote phenotypic maturation and cytokine/chemokine production by human DCs. We also found that COL markedly augments the ability of murine BM-DCs to cross-present exogenous protein antigens to CD8 T cells. At least two key questions, however, remain to be addressed experimentally. Does COL treatment also enhance antigen cross-presentation by human DCs? Can we use COL (or COL-pretreated DCs) to promote cross-presentation of tumor-associated antigens or microbial antigens in vivo? Nevertheless, this study suggests a previously unrecognized pharmacological activity of COL, which should be taken into consideration when administering COL to patients with inflammatory skin disorders.

Allogeneic T cells, Behcet disease, Colchicine (COL), Dendritic Cells, Epidermal Langerhans cells, Inflammatory skin diseases, Leukocytoclastic vasculitis, Microtubule depolymerizing drug, Palmoplantar pustulosis, Psoriasis, Sweet’s syndrome