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Articles by K Shortman
Total Records ( 1 ) for K Shortman
  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

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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