Nicotine Exposure Alters the mRNA Expression of Notch Ligands in Dendritic Cells and Their Response to Th1‐/Th2‐Promoting Stimuli

• Published in: Scandinavian journal of immunology 2015-02, Vol.81 (2), p.110-120
• Main Authors: Nouri‐Shirazi, M., Kahlden, C., Nishino, P., Guinet, E.
• Format: Article
• Language: English
• Subjects: Animals; B7-1 Antigen - immunology; B7-1 Antigen - metabolism; B7-2 Antigen - immunology; B7-2 Antigen - metabolism; Calcium-Binding Proteins - genetics; Calcium-Binding Proteins - immunology; Calcium-Binding Proteins - metabolism; Cells, Cultured; Dendritic Cells - immunology; Dendritic Cells - metabolism; Gene Expression - drug effects; Gene Expression - immunology; Humans; Intercellular Signaling Peptides and Proteins - genetics; Intercellular Signaling Peptides and Proteins - immunology; Intercellular Signaling Peptides and Proteins - metabolism; Interleukin-10 - immunology; Interleukin-10 - metabolism; Interleukin-12 - immunology; Interleukin-12 - metabolism; Interleukin-4 - immunology; Interleukin-4 - metabolism; Interleukin-4 - pharmacology; Intracellular Signaling Peptides and Proteins - genetics; Intracellular Signaling Peptides and Proteins - immunology; Intracellular Signaling Peptides and Proteins - metabolism; Jagged-1 Protein; Jagged-2 Protein; Ligands; Membrane Proteins - genetics; Membrane Proteins - immunology; Membrane Proteins - metabolism; Mice, Inbred BALB C; Nicotine - immunology; Nicotine - pharmacology; Nicotinic Agonists - immunology; Nicotinic Agonists - pharmacology; Receptors, Notch - immunology; Receptors, Notch - metabolism; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; RNA, Messenger - immunology; RNA, Messenger - metabolism; Serrate-Jagged Proteins; Th1 Cells - immunology; Th1 Cells - metabolism; Th2 Cells - immunology; Th2 Cells - metabolism
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.12254

Dendritic cells (DCs) utilize polarizing signals to instruct the differentiation of T helper (Th) cells into Th1 and Th2 effector cells: antigen‐specific ‘signal 1’, costimulatory ‘signal 2’ and polarizing cytokines ‘signal 3’. Accumulating evidence suggests the involvement of an additional signal, the Notch signalling pathway. We reported that in response to Th1‐promoting stimuli, both mouse and human DCs generated in the presence of the immune modulator nicotine (nicDCs) fail to support the development of effector memory Th1 cells. However, in response to Th2‐promoting stimuli, these nicDCs preferentially support the differentiation of antigen‐specific IL‐4‐producing Th2 effector cells. Here, we show that when compared to their control counterparts, immature mouse and human nicDCs display higher levels of the Notch ligands D1, D4 and J2 mRNA expression. In response to Th1‐ and Th2‐promoting stimuli, mouse nicDCs display higher levels of the Notch ligands D1, D4 and J2, while human nicDCs show higher levels of D1, D4 and J1 mRNA expression. Furthermore, both stimulated mouse and human nicDCs express higher CD86 to CD80 ratio and produce lower amount of IL‐12. Collectively, our data suggest that these changes in addition to an increase in Jagged expression correlate with the ability of nicDCs to modulate the Th1/Th2 balance in favour of Th2 generation.