GILZ expression in human dendritic cells redirects their maturation and prevents antigen-specific T lymphocyte response.
Interleukin (IL)-10 and glucocorticoids (GCs) inhibit the ability of antigen-presenting dendritic cells (DCs) to stimulate T lymphocytes. We show that induction of GILZ (GC-induced leucine zipper) is involved in this phenomenon. IL-10, dexamethasone (DEX), and transforming growth factor (TGF)beta stimulate GILZ production in human immature DCs derived from monocytes and from CD34+ cells. GILZ is necessary and sufficient for DEX, IL-10, and TGFbeta modulation of CD80, CD83, CD86, immunoglobulin-like transcript (ILT)-3, and B7-H1 expression by DCs, and alteration of DC functions. GILZ stimulates the production of IL-10 by immature DCs and prevents the production of inflammatory chemokines by CD40L-activated DCs. In contrast, GILZ does not prevent CD40 ligand-mediated inhibition of phagocytosis, indicating that it affects some but not all aspects of DC maturation. GILZ prevents DCs from activating antigen-specific T lymphocyte responses. Administration of GCs to patients stimulates GILZ expression in their circulating antigen-presenting cells, and this contributes to the weak lymphocyte responses of GC-treated patients. Thus, regulation of GILZ expression is an important factor determining the decision of DCs whether or not to stimulate T lymphocytes, and IL-10, GCs, and TGFbeta share this mechanism for influencing DC functions and the balance between immune response and tolerance.
Cohen
Nicolas
N
INSERM UMR-S764, Service d'Hépato-Gastro-Entérologie and Service de Microbiologie--Immunologie Biologique, Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Institut Paris-Sud sur les Cytokines, Université Paris-Sud, Clamart, France.
Mouly
Enguerran
E
Hamdi
Haifa
H
Maillot
Marie-Christine
MC
Pallardy
Marc
M
Godot
Véronique
V
Capel
Francis
F
Balian
Axel
A
Naveau
Sylvie
S
Galanaud
Pierre
P
Lemoine
François M
FM
Emilie
Dominique
D
D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000494:pharmacology; D015703:Antigens, CD / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000494:pharmacology; D003713:Dendritic Cells / Q000276:immunology*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014157:Transcription Factors / Q000096:biosynthesis / Q000276:immunology*
D000893:Anti-Inflammatory Agents; D015703:Antigens, CD; D016207:Cytokines; C404226:TSC22D3 protein, human; D014157:Transcription Factors