TY - JOUR
T1 - Mouse CD8alpha+ DCs and human BDCA3+ DCs are major producers of IFN-lambda in response to poly IC.
AU - Lauterbach, Henning
AU - Bathke, Barbara
AU - Gilles, Stefanie
AU - Traidl-Hoffmann, Claudia
AU - Luber, Christian A.
AU - Fejer, György
AU - Freudenberg, Marina A.
AU - Davey, Gayle M.
AU - Vremec, David
AU - Kallies, Axel
AU - Wu, Li
AU - Shortman, Ken
AU - Chaplin, Paul
AU - Suter, Mark
AU - O'Keeffe, Meredith
AU - Hochrein, Hubertus
PY - 2010/11/22
Y1 - 2010/11/22
N2 - 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.
AB - 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.
KW - Animals
KW - Antigens
KW - Surface
KW - CD8 Antigens
KW - Cytokines
KW - Dendritic Cells
KW - Herpesvirus 2
KW - Human
KW - Humans
KW - Interferon Inducers
KW - Interferon Regulatory Factor-3
KW - Interferon Regulatory Factor-7
KW - Interferon Regulatory Factors
KW - Interferons
KW - Interleukin-12
KW - Interleukins
KW - Mice
KW - Parapoxvirus
KW - Poly I-C
KW - Thrombomodulin
KW - Toll-Like Receptor 3
UR - https://pearl.plymouth.ac.uk/context/bhs-research/article/1060/viewcontent/Mouse_20CD8alpha__20DCs_20and_20human_20BDCA3__20DCs_20are_20major_20producers_20of_20IFN_lambda_20in_20response_20to_20poly_20IC.pdf
U2 - 10.1084/jem.20092720
DO - 10.1084/jem.20092720
M3 - Article
SN - 1540-9538
VL - 207
SP - 2703
EP - 2717
JO - J Exp Med
JF - J Exp Med
IS - 12
ER -
