Cysteinyl-leukotriene receptor type 1 expression and function is down-regulated during monocyte-derived dendritic

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Maryse Thivierge1, Jana Stankova, Marek Rola-Pleszczynski

  • 1Immunology Division, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

Journal of Immunology (Baltimore, Md. : 1950)
|October 23, 2009
PubMed

Insights

Zymosan, a TLR2 agonist, reduces cysteinyl-leukotriene receptor type 1 (CysLT1) expression and function on dendritic cells (DCs). This modulation is partly mediated by prostaglandin E2 (PGE2) and IL-10, impacting adaptive immune responses.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Toll-like receptors (TLRs) activate dendritic cells (DCs) to initiate adaptive immunity.
  • Leukotrienes modulate DC functions, and DCs express cysteinyl-leukotriene receptor type 1 (CysLT1).

Purpose of the Study:

  • To investigate how zymosan, a TLR2 agonist, affects CysLT1 expression and function on human monocyte-derived DCs.
  • To elucidate the mechanisms underlying zymosan-induced modulation of CysLT1.

Main Methods:

  • Human monocyte-derived DCs were differentiated and matured with zymosan.
  • CysLT1 mRNA and protein levels were measured.
  • DC functional responses (calcium mobilization, cytokine production, chemotaxis) to leukotriene D4 were assessed.
  • The roles of TLR2, dectin-1, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), IL-10, and MAPK pathways were investigated.

Main Results:

  • Zymosan significantly reduced CysLT1 mRNA and protein expression in DCs in a time-dependent manner.
  • DC functional responsiveness to leukotriene D4 was diminished following zymosan maturation.
  • Zymosan-induced CysLT1 down-regulation was mediated by TLR2 and dectin-1 activation.
  • Zymosan increased COX-2 expression and production of PGE2 and IL-10.
  • Inhibition of IL-10 or COX pathways partially blocked zymosan's effect on CysLT1.
  • IL-10 and PGE2 could reproduce the down-regulation of CysLT1, dependent on MAPK activation.

Conclusions:

  • Zymosan down-regulates CysLT1 expression and function in DCs, reducing their responsiveness to leukotriene D4.
  • This effect is partly mediated by the endogenous production of PGE2 and IL-10 by DCs.
  • The findings highlight a novel mechanism by which TLR activation influences DC function and immune cell communication.

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