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

First Page

2703

Last Page

2717

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

Download

Share

COinS