Differential modulation of cysteinyl leukotriene receptor 1 and 2 expression by distinct Toll-like receptor agonists in monocyte-derived dendritic cells

Background

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.

Objectives

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.

Results

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.

Conclusion

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.