Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function

Jens Dannull, Tristan Schneider, Walter T. Lee, Nicole De Rosa, Douglas Tyler, Scott K. Pruitt

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Generation of human monocyte-derived dendritic cells (DCs) for cancer vaccination involves ex vivo maturation in the presence of proinflammatory cytokines and prostaglandin E(2) (PGE2). Although the inclusion of PGE2 during maturation is imperative for the induction of DC migration, PGE2 has unfavorable effects on the immunostimulatory capacity of these cells. Like PGE2, leukotrienes (LTs) are potent mediators of DC migration. We therefore sought to characterize the migratory and immunologic properties of DCs that matured in the presence of LTB4, LTC4, LTD4, and PGE2. Here, we demonstrate that DCs matured in the presence of LTC4, but not LTB4 or LTD4, are superior to PGE2-matured DCs in stimulating CD4+ T-cell responses and in inducing antigen-specific cytotoxic T lymphocytes (CTLs) in vitro without concomitant induction or recruitment of regulatory T cells (Tregs). LTC4-matured DCs migrate efficiently through layers of extracellular matrix and secrete higher levels of immunostimulatory IL-12p70 while producing reduced levels of immuneinhibitory IL-10, IL12p40, indoleamine-2,3-dioxidase, and TIMP-1 (tissue inhibitor of matrix metalloproteinases). Intracellular calcium mobilization and receptor antagonist studies reveal that, in contrast to LTD4, LTC4 did not signal through CysLTR1 in DCs. Collectively, our data suggest that LTC4 represents a promising candidate to replace PGE 2 in DC maturation protocols for cancer vaccination.

Original languageEnglish (US)
Pages (from-to)3113-3122
Number of pages10
JournalBlood
Volume119
Issue number13
DOIs
StatePublished - Mar 29 2012
Externally publishedYes

Fingerprint

Leukotriene C4
Dendritic Cells
Monocytes
Prostaglandins E
Leukotriene D4
T-cells
Leukotriene B4
Cell Movement
Vaccination
Calcium-Sensing Receptors
Tissue Inhibitor of Metalloproteinases
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase Inhibitors
Leukotrienes
Cytotoxic T-Lymphocytes
Regulatory T-Lymphocytes
Interleukin-10
Extracellular Matrix
Neoplasms
Tissue

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function. / Dannull, Jens; Schneider, Tristan; Lee, Walter T.; De Rosa, Nicole; Tyler, Douglas; Pruitt, Scott K.

In: Blood, Vol. 119, No. 13, 29.03.2012, p. 3113-3122.

Research output: Contribution to journalArticle

Dannull, Jens ; Schneider, Tristan ; Lee, Walter T. ; De Rosa, Nicole ; Tyler, Douglas ; Pruitt, Scott K. / Leukotriene C4 induces migration of human monocyte-derived dendritic cells without loss of immunostimulatory function. In: Blood. 2012 ; Vol. 119, No. 13. pp. 3113-3122.
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