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The Journal of Experimental Medicine

Year: 2010  |  Volume: 207  |  Issue: 12  |  Page No.: 2703 - 2717

Mouse CD8{alpha}+ DCs and human BDCA3+ DCs are major producers of IFN-{lambda} in response to poly IC

H Lauterbach, B Bathke, S Gilles, C Traidl Hoffmann, C. A Luber, G Fejer, M. A Freudenberg, G. M Davey, D Vremec, A Kallies, L Wu, K Shortman, P Chaplin, M Suter, M O'Keeffe and H. Hochrein

Abstract

Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-s (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-, 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- production by splenocytes segregated with cells phenotypically resembling CD8+ conventional dendritic cells (DCs [cDCs]). In vitro experiments revealed that CD8+ cDCs were the major producers of IFN- in response to poly IC, whereas both CD8+ cDCs and plasmacytoid DCs produced large amounts of IFN- in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8+ cDCs produced IFN- or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8+ DCs, also produced large amounts of IFN- upon poly IC stimulation. Thus, IFN- production in response to poly IC is a novel function of mouse CD8+ cDCs and their human equivalents.

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