Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells.
Dendritic cells (DCs) can initiate and shape host immune responses toward either immunity or tolerance by their effects on antigen-specific CD4(+) T cells. DC-asialoglycoprotein receptor (DC-ASGPR), a lectinlike receptor, is a known scavenger receptor. Here, we report that targeting antigens to human DCs via DC-ASGPR, but not lectin-like oxidized-LDL receptor, Dectin-1, or DC-specific ICAM-3-grabbing nonintegrin favors the generation of antigen-specific suppressive CD4(+) T cells that produce interleukin 10 (IL-10). These findings apply to both self- and foreign antigens, as well as memory and naive CD4(+) T cells. The generation of such IL-10-producing CD4(+) T cells requires p38/extracellular signal-regulated kinase phosphorylation and IL-10 induction in DCs. We further demonstrate that immunization of nonhuman primates with antigens fused to anti-DC-ASGPR monoclonal antibody generates antigen-specific CD4(+) T cells that produce IL-10 in vivo. This study provides a new strategy for the establishment of antigen-specific IL-10-producing suppressive T cells in vivo by targeting whole protein antigens to DCs via DC-ASGPR.
Baylor Institute for Immunology Research, Dallas, TX 75204, USA.
Dapeng
D
Li
Gabrielle
G
Romain
Anne-Laure
AL
Flamar
Dorothée
D
Duluc
Melissa
M
Dullaers
Xiao-Hua
XH
Li
Sandra
S
Zurawski
Nathalie
N
Bosquet
Anna Karolina
AK
Palucka
Roger
R
Le Grand
Anne
A
O'Garra
Gerard
G
Zurawski
Jacques
J
Banchereau
Sangkon
S
Oh
D000818:Animals; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D037263:Asialoglycoprotein Receptor / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D008024:Ligands; D008251:Macaca; D008297:Male; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D015398:Signal Transduction
D000941:Antigens; D037263:Asialoglycoprotein Receptor; D008024:Ligands; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D016753:Interleukin-10; D048049:Extracellular Signal-Regulated MAP Kinases