Differential modulation of cysteinyl leukotriene receptor 1 and 2 expression by distinct Toll-like receptor agonists in monocyte-derived dendritic cells
© The Author(s) 2004
Published: 13 September 2004
Dendritic cells (DC) acquire, during their maturation, the expression of the chemokine receptor CCR7 and the ability to migrate to lymph nodes in response to MIP3 beta (CCL19). This migration is impaired in mice lacking the leukotriene (LT) C4 transporter and is restored by addition of exogenous LTC4.
To further define the role of LT in human DC function, we studied their expression of LT receptors during their differentiation from monocytes and their maturation.
Monocyte-derived immature DC had a lower expression of the LTD4 receptor (CysLT1) than monocytes, whereas their expression of the LTC4/LTD4 (CysLT2) and the LTB4 (BLT1) receptors remained stable. Maturation of DC with lipopolysaccharide, a classical Toll-like receptor (TLR)4 agonist, reduced CysLT1 expression by a further 50%, whereas CysLT2 expression was increased and BLT1 expression was only marginally reduced. Zymosan, a TLR2 agonist, reduced all receptor levels, whereas the TLR3 agonist poly I:C had no effect on CysLT expression. LTC4, more than LTD4, was able to enhance human DC migration in response to CCL19 and promote DC activation of T-cell proliferation, when DC were matured with lipopolysaccharide or zymosan, but not polyI:C.
Our data suggest that human DC may differentially respond to LT, depending on their maturational stimuli, and thus potentially affect both innate and adaptive immunity in the context of inflammation.
Supported by grants from the Canadian Institutes of Health Research (MR-P and JS) and a Canada Research Chair in Inflammation (MR-P).