Interferon-beta induces the development of type 2 dendritic cells.
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)-beta used for treatment of multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system with possible autoimmune origin. How IFN-beta 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-beta 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-3Ralpha). IFN-beta dose-dependently increased IL-3Ralpha+ DCs and decreased CD1a+ DCs. After 7 days' culture with IFN-beta at a concentration of 10 000 U/ml, more than 40% of DCs expressed IL-3Ralpha. IFN-beta, together with GM-CSF and IL-4, also induced maturation of IL-3Ralpha-expressing cells, as reflected by upregulation of HLA-DR and of the costimulatory molecules CD40, CD80 and CD86. In contrast to control DCs, IFN-beta-treated DCs produced predominantly IL-10 but only low levels of IL-12p40. Correspondingly, IFN-beta-treated DCs strongly suppressed IFN-gamma production but enhanced IL-10 production by allogeneic blood mononuclear cells. Our data suggest that IFN-beta in vitro can induce the development of DC2, which provide a permissive environment for Th2 differentiation. This finding represents a novel mechanism for action of IFN-beta in MS.
Neuroimmunology Unit, Division of Neurology, Huddinge University Hospital, Karolinska Institute, Stockholm, Sweden. yu-min.huang@neurotec.ki.se
Y M
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Huang
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Hussien
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Yarilin
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BG
Xiao
Y J
YJ
Liu
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D018949:Antigens, CD1 / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism* / Q000494:pharmacology; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D007962:Leukocytes / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D011994:Recombinant Proteins / Q000378:metabolism; D018417:Th1 Cells / Q000378:metabolism; D018418:Th2 Cells / Q000378:metabolism; D013997:Time Factors
D018949:Antigens, CD1; C419393:CD1a antigen; D011994:Recombinant Proteins; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D016899:Interferon-beta; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor