| First Author | Lauterbach H | Year | 2010 |
| Journal | J Exp Med | Volume | 207 |
| Issue | 12 | Pages | 2703-17 |
| PubMed ID | 20975040 | Mgi Jnum | J:176879 |
| Mgi Id | MGI:5292849 | Doi | 10.1084/jem.20092720 |
| Citation | Lauterbach H, et al. (2010) Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC. J Exp Med 207(12):2703-17 |
| abstractText | Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-lambdas (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-lambda, 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-lambda production by splenocytes segregated with cells phenotypically resembling CD8alpha(+) conventional dendritic cells (DCs [cDCs]). In vitro experiments revealed that CD8alpha(+) cDCs were the major producers of IFN-lambda in response to poly IC, whereas both CD8alpha(+) cDCs and plasmacytoid DCs produced large amounts of IFN-lambda in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8alpha(+) cDCs produced IFN-lambda or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8alpha(+) DCs, also produced large amounts of IFN-lambda upon poly IC stimulation. Thus, IFN-lambda production in response to poly IC is a novel function of mouse CD8alpha(+) cDCs and their human equivalents. |
