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

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.

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 Creators:
Lauterbach, Henning, Author
Bathke, Barbara, Author
Gilles, Stefanie, Author
Traidl-Hoffmann, Claudia, Author
Luber, Christian A., Author
Fejer, György1, Author           
Freudenberg, Marina A.1, Author           
Davey, Gayle M., Author
Vremec, David, Author
Kallies, Axel, Author
Wu, Li, Author
Shortman, Ken, Author
Chaplin, Paul, Author
Suter, Mark, Author
O'Keeffe, Meredith, Author
Hochrein, Hubertus, Author
Affiliations:
1Department of Developmental Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243647              

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 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.

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Language(s): eng - English
 Dates: 2010-10-25
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 529864
ISI: 000285505000015
 Degree: -

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Title: Journal of Experimental Medicine
  Alternative Title : J. Exp. Med.
Source Genre: Journal
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Publ. Info: NEW YORK : ROCKEFELLER UNIV PRESS
Pages: - Volume / Issue: 207 (12) Sequence Number: - Start / End Page: 2703 - 2717 Identifier: ISSN: 0022-1007