INTERFERON-BETA INDUCES THE DEVELOPMENT OF TYPE 2 DENDRITIC CELLS

• Published in: Cytokine (Philadelphia, Pa.) Vol. 13; no. 5; pp. 264 - 271
• Main Authors: Huang, Yu-Min, Hussien, Yassir, Yarilin, Dmitry, Xiao, Bao-Guo, Liu, Yong-Jun, Link, Hans
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 07.03.2001
• Subjects: Antigens, CD1 - metabolism; Cell Differentiation; Cell Division; Coculture Techniques; Dendritic Cells - metabolism; Dendritic Cells - physiology; dendritic cells/IFN-β/multiple sclerosis; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Humans; Interferon-beta - metabolism; Interferon-beta - pharmacology; Interferon-gamma - biosynthesis; Interleukin-10 - biosynthesis; Interleukin-12 - antagonists & inhibitors; Interleukin-12 - biosynthesis; Interleukin-4 - pharmacology; Leukocytes - metabolism; Medicin och hälsovetenskap; Monocytes - metabolism; Phenotype; Recombinant Proteins - metabolism; Th1 Cells - metabolism; Th2 Cells - metabolism; Time Factors; dendritic cells/IFN-β/multiple sclerosis
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.2000.0835

Suppression of interleukin 12 (IL-12) production by dendritic cells (DCs) has been hypothesized to be a principal mechanism underlying the biological action of interferon (IFN)-β used for treatment of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system with possible autoimmune origin. How IFN-β interacts with DCs to inhibit IL-12 production remains unclear. In this study, we found that DCs derived from human blood monocytes, upon culture in the presence of IFN-β with granulocyte-macrophage colony- stimulating factor (GM-CSF) and IL-4, differentiated into a population expressing CD14−CD1a−HLA-DR+. This population expressed CD123 (IL-3Rα). IFN-β dose-dependently increased IL-3Rα+DCs and decreased CD1a+DCs. After 7 days' culture with IFN-β at a concentration of 10000U/ml, more than 40% of DCs expressed IL-3Rα. IFN-β, together with GM-CSF and IL-4, also induced maturation of IL-3Rα-expressing cells, as reflected by upregulation of HLA-DR and of the costimulatory molecules CD40, CD80 and CD86. In contrast to control DCs, IFN-β-treated DCs produced predominantly IL-10 but only low levels of IL-12p40. Correspondingly, IFN-β-treated DCs strongly suppressed IFN-γ production but enhanced IL-10 production by allogeneic blood mononuclear cells. Our data suggest that IFN-β in vitro can induce the development of DC2, which provide a permissive environment for Th2differentiation. This finding represents a novel mechanism for action of IFN-β in MS.