Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells

Dapeng Li, Gabrielle Romain, Anne Laure Flamar, Dorothée Duluc, Melissa Dullaers, Xiao Hua Li, Sandra Zurawski, Nathalie Bosquet, Anna Karolina Palucka, Roger Le Grand, Anne O'Garra, Gerard Zurawski, Jacques Banchereau, SangKon Oh

Research output: Contribution to journalArticle

106 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)109-121
Number of pages13
JournalJournal of Experimental Medicine
Volume209
Issue number1
DOIs
StatePublished - Jan 1 2012
Externally publishedYes

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Autoantigens
Interleukin-10
Dendritic Cells
T-Lymphocytes
Antigens
CD4 Antigens
Oxidized LDL Receptors
Asialoglycoprotein Receptor
Scavenger Receptors
Extracellular Signal-Regulated MAP Kinases
Protein Transport
Lectins
Primates
Immunity
Immunization
Monoclonal Antibodies
Phosphorylation

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 journalArticle

Li, D, Romain, G, Flamar, AL, Duluc, D, Dullaers, M, Li, XH, Zurawski, S, Bosquet, N, Palucka, AK, Le Grand, R, O'Garra, A, Zurawski, G, Banchereau, J & Oh, S 2012, 'Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells', Journal of Experimental Medicine, vol. 209, no. 1, pp. 109-121. https://doi.org/10.1084/jem.20110399
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. / Targeting self- and foreign antigens to dendritic cells via DC-ASGPR generates IL-10-producing suppressive CD4+ T cells. In: Journal of Experimental Medicine. 2012 ; Vol. 209, No. 1. pp. 109-121.
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