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

作者：Nouri Shirazi M^*; Kahlden C; Nishino P; Guinet E

来源：Scandinavian Journal of Immunology, 2015, 81(2): 110-120.

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.

• 出版日期2015-2