ORCID

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.

DOI

10.1084/jem.20092720

Publication Date

2010-11-22

Publication Title

J Exp Med

Volume

207

Issue

12

Organisational Unit

School of Biomedical Sciences

Keywords

Animals, Antigens, Surface, CD8 Antigens, Cytokines, Dendritic Cells, Herpesvirus 2, Human, Humans, Interferon Inducers, Interferon Regulatory Factor-3, Interferon Regulatory Factor-7, Interferon Regulatory Factors, Interferons, Interleukin-12, Interleukins, Mice, Parapoxvirus, Poly I-C, Thrombomodulin, Toll-Like Receptor 3

First Page

2703

Last Page

2717

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