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Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC

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Fejer,  György
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Freudenberg,  Marina A.
Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Lauterbach, H., Bathke, B., Gilles, S., Traidl-Hoffmann, C., Luber, C. A., Fejer, G., et al. (2010). Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC. Journal of Experimental Medicine, 207(12), 2703-2717.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002B-8E71-9
Abstract
Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-λs (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-λ, which depended on hematopoietic cells and the presence of TLR3 (Toll-like receptor 3), IRF3 (IFN regulatory factor 3), IRF7, IFN-I receptor, Fms-related tyrosine kinase 3 ligand (FL), and IRF8 but not on MyD88 (myeloid differentiation factor 88), Rig-like helicases, or lymphocytes. Upon poly IC injection in vivo, the IFN-λ production by splenocytes segregated with cells phenotypically resembling CD8α+ conventional dendritic cells (DCs [cDCs]). In vitro experiments revealed that CD8α+ cDCs were the major producers of IFN-λ in response to poly IC, whereas both CD8α+ cDCs and plasmacytoid DCs produced large amounts of IFN-λ in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8α+ cDCs produced IFN-λ or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8α+ DCs, also produced large amounts of IFN-λ upon poly IC stimulation. Thus, IFN-λ production in response to poly IC is a novel function of mouse CD8α+ cDCs and their human equivalents.