Nickel and DNCB Induce CCR7 Expression on Human Dendritic Cells Through Different Signalling Pathways: Role of TNF-α and MAPK

• Published in: Journal of investigative dermatology Vol. 123; no. 3; pp. 494 - 502
• Main Authors: Boislève, Fanny, Kerdine-Römer, Saadia, Rougier-Larzat, Nathalie, Pallardy, Marc
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.09.2004; Nature Publishing
• Subjects: Antigens, CD34 - metabolism; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Biological and medical sciences; Chemokine CCL19; Chemokines, CC - metabolism; Chemokines, CC - pharmacology; contact hypersensitivity; Dendritic Cells - drug effects; Dendritic Cells - physiology; Dermatology; Dinitrochlorobenzene - pharmacology; Down-Regulation; Female; Fetal Blood; hapten; Haptens - metabolism; Humans; Interleukin-1 - metabolism; Irritants - pharmacology; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System - drug effects; MAP Kinase Signaling System - physiology; Medical sciences; migration; Mitogen-Activated Protein Kinases - antagonists & inhibitors; Mitogen-Activated Protein Kinases - metabolism; Nickel - pharmacology; p38 Mitogen-Activated Protein Kinases; Phenotype; Receptors, CCR7; Receptors, Chemokine - genetics; RNA, Messenger - analysis; signal transduction; Tumor Necrosis Factor-alpha - metabolism; Tumor Necrosis Factor-alpha - pharmacology; migration; hapten; signal transduction; contact hypersensitivity; Human; Dendritic cell; Enzyme; Dermatology; Mitogen-activated protein kinase; Chemokine receptor; CC chemokine; Dinitrochlorobenzene; contact hypersensitivity/hapten/migration/signal transduction; Signal transduction; Antigen presenting cell; CCR7 chemokine receptor; Nickel; Tumor necrosis factor α
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/j.0022-202X.2004.23229.x

After application of haptens on the skin, immature dendritic cells (DC), also named Langerhans cells (LC), migrate to the draining lymph node to sensitize naïve T-lymphocytes. Migration of DC involves many factors including the Cys-Cys chemokine receptor, CCR7. We investigated the effects of two well-known haptens, dinitrochlorobenzene (DNCB) and nickel (NiSO4), on the expression of CCR7 on human DC derived from CD34+ progenitor cells. Both haptens were able to induce CCR7 expression and DC migration in response to Cys-Cys chemokine ligand, CCL19. Since interleukin (IL)-1β and tumor necrosis factor (TNF)-α have been shown to participate in LC migration during contact hypersensitivity, we tested the effect of their neutralization on CCR7 expression. Neutralization of IL-1β activity did not modify CCR7 expression in response to both haptens. CCR7 expression was strongly dependent on TNF-α in the case of DNCB, however, neutralization of TNF-α only partially reduced CCR7 expression upon NiSO4 treatment. DNCB, NiSO4 and TNF-α activated p38 mitogen-activated protein kinases (MAPK) and c-jun N-terminal kinase (JNK). Both p38 MAPK and JNK participated to TNF-α production induced by DNCB. Inhibition of both p38 MAPK and JNK affected significantly CCR7 expression upon nickel treatment whereas only inhibition of p38 MAPK but not of JNK downregulated CCR7 in the case of TNF-α stimulation. These results suggest that MAPK are necessary for haptens to induce CCR7 expression. NiSO4, however, activates directly CCR7 expression through p38 MAPK and JNK activation whereas DNCB needs TNF-α whose secretion is also regulated by p38 MAPK and JNK.