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Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells.

Abstract：

:Peroxisome proliferator-activated receptor gamma (PPARgamma ), a member of the nuclear receptor superfamily, has recently been described as a modulator of macrophage functions and as an inhibitor of T cell proliferation. Here, we investigated the role of PPARgamma in dendritic cells (DC), the most potent antigen-presenting cells. We showed that PPARgamma is highly expressed in immature human monocyte-derived DC (MDDC) and that it may affect the immunostimulatory function of MDDC stimulated with lipopolysaccharide (LPS) or via CD40 ligand (CD40L). We found that the synthetic PPARgamma agonist rosiglitazone (as well as pioglitazone and troglitazone) significantly increases on LPS- and CD40L-activated MDDC, the surface expression of CD36 (by 184% and 104%, respectively) and CD86 (by 54% and 48%), whereas it reduces the synthesis of CD80 (by 42% and 42%). Moreover, activation of PPARgamma resulted in a dramatic decreased secretion of the Th1-promoting factor IL-12 in LPS- and CD40L-stimulated cells (by 47% and 62%), while the production of IL-1beta, TNF-alpha, IL-6 and IL-10 was unaffected. Finally, PPARgamma ligands down-modulate the synthesis of IFN-gamma -inducible protein-10 (recently termed as CXCL10) and RANTES (CCL5), both chemokines involved in the recruitment of Th1 lymphocytes (by 49% and 30%), but not the levels of the Th2 cell-attracting chemokines,macrophage-derived chemokine (CCL22) and thymus and activation regulated chemokine (CCL17), in mature MDDC. Taken together, our data suggest that activation of PPARgamma in human DC may have an impact in the orientation of primary and secondary immune responses by favoring type 2 responses.

journal_name

Eur J Immunol

journal_title

European journal of immunology

authors

Gosset P,Charbonnier AS,Delerive P,Fontaine J,Staels B,Pestel J,Tonnel AB,Trottein F

doi

10.1002/1521-4141(2001010)31:10<2857::aid-immu2857

keywords:

subject

Has Abstract

pub_date

2001-10-01 00:00:00

pages

2857-65

issue

eissn

0014-2980

issn

1521-4141

pii

10.1002/1521-4141(2001010)31:10<2857::AID-IMMU2857

journal_volume

pub_type

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Peroxisome proliferator-activated receptor gamma activators affect the maturation of human monocyte-derived dendritic cells.