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Differential Regulation of Notch Ligands in Dendritic Cells upon Interaction with T Helper Cells
Author(s) -
Sauma D.,
Espejo P.,
Ramirez A.,
Fierro A.,
Rosemblatt M.,
Bono M. R.
Publication year - 2011
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/j.1365-3083.2011.02541.x
Subject(s) - notch signaling pathway , microbiology and biotechnology , cd40 , t helper cell , antigen presenting cell , biology , t cell , chemistry , immune system , signal transduction , immunology , cytotoxic t cell , in vitro , genetics
The Notch signalling pathway has recently been linked to T helper 1 (Th1)/T helper 2 (Th2) cell polarization via a mechanism involving differential expression of Notch ligands, Delta‐like and Jagged, in antigen‐presenting cells. However, whether stimuli other than pathogen‐derived factors are involved in the regulation of Notch ligand expression in dendritic cells (DCs) remains unknown. Here, we address the effect of T helper cells (Th1 and Th2) on Delta‐like 4 and Jagged 2 expression in bone marrow–derived DCs. We demonstrate that both Th1 and Th2 cells induce Delta‐like 4 mRNA expression in DCs, in a process that is, in part, mediated by CD40 signalling. In contrast, only Th2 cells induce a significant increase in Jagged 2 mRNA levels in DCs. Additionally, we show that IL‐4, a hallmark Th2 cytokine, plays a role in Jagged 2 expression, as evidenced by the fact that cholera toxin, a Th2‐promoting stimulus, induces Jagged 2 mRNA expression in DCs only in the presence of IL‐4. Finally, we demonstrate that DCs also express Notch 1 and that this expression is downregulated by IL‐4. These data suggest that Notch ligands are differentially regulated in DCs: Delta‐like 4 is regulated by T helper cells and by pathogen‐derived Th1 stimuli, whereas Jagged 2 is regulated by Th2 cells and pathogen‐derived Th2‐promoting stimuli. Based on our results, we propose that the positive feedback loop that Th2 cells exert on T cell polarization may involve the induction of Jagged 2 expression in DCs.