Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 109-121 |
| Number of pages | 13 |
| Journal | Journal of Experimental Medicine |
| Volume | 209 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2012 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
Cite this
Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells. / Li, Dapeng; Romain, Gabrielle; Flamar, Anne Laure; Duluc, Dorothée; Dullaers, Melissa; Li, Xiao Hua; Zurawski, Sandra; Bosquet, Nathalie; Palucka, Anna Karolina; Le Grand, Roger; O'Garra, Anne; Zurawski, Gerard; Banchereau, Jacques; Oh, SangKon.
In: Journal of Experimental Medicine, Vol. 209, No. 1, 01.01.2012, p. 109-121.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells
AU - Li, Dapeng
AU - Romain, Gabrielle
AU - Flamar, Anne Laure
AU - Duluc, Dorothée
AU - Dullaers, Melissa
AU - Li, Xiao Hua
AU - Zurawski, Sandra
AU - Bosquet, Nathalie
AU - Palucka, Anna Karolina
AU - Le Grand, Roger
AU - O'Garra, Anne
AU - Zurawski, Gerard
AU - Banchereau, Jacques
AU - Oh, SangKon
PY - 2012/1/1
Y1 - 2012/1/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84863116620&partnerID=8YFLogxK
U2 - 10.1084/jem.20110399
DO - 10.1084/jem.20110399
M3 - Article
C2 - 22213806
AN - SCOPUS:84863116620
VL - 209
SP - 109
EP - 121
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 1
ER -