Induction of tolerogenic vs immunogenic dendritic cells (DCs) in the presence of GM-CSF is regulated by the strength of signaling from monophosphoryl lipid A (MPLA) in association with glutathione and fetal hemoglobin gamma-chain

Khatri I., Alexander C., Brandenburg K., Fournier K., Mach J. P., Rietschel E. T., ...Daha Fazla

IMMUNOLOGY LETTERS, cilt.124, sa.1, ss.44-49, 2009 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 124 Sayı: 1
  • Basım Tarihi: 2009
  • Doi Numarası: 10.1016/j.imlet.2009.04.002
  • Dergi Adı: IMMUNOLOGY LETTERS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.44-49
  • Anahtar Kelimeler: Gamma-chain of fetal hemoglobin (Hgb gamma), CD4(+)CD25(+)Treg, MPLA, CD200R, Dendritic cells, Immunoregulation, Treg, TLR, TOLL-LIKE RECEPTORS, PRODUCTION IN-VIVO, T-CELLS, CYTOKINE PRODUCTION, AGED MICE, FLT3 LIGAND, SKIN-GRAFTS, CD4(+) TREG, TGF-BETA, EXPRESSION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Previous studies showed a fetal sheep liver extract (FSLE), in association with monophosphoryl lipid A, MPLA (a bioactive component of lipid A of LPS), could interact to induce the development of dendritic cells (DCs) which regulated production of Foxp3(+) Treg. This interaction was associated with an altered gene expression both of distinct subsets of TLRs and of CD200Rs. Prior studies had suggested that major interacting components within FSLE were gamma-chain of fetal hemoglobin (Hgb gamma) and glutathione (GSH). We investigated whether differentiation/maturation of DCs in vitro in the presence of either GMCSF or Flt3L to produce preferentially either immunogenic or tolerogenic DCs was itself controlled by an interaction between MPLA, GSH and Hgb gamma. At low (similar to 10 mu g/ml) Hgb gamma concentrations, DCs developing in culture with GSH and MPLA produced optimal stimulation of allogeneic CTL cell responses in vitro (and enhanced skin graft rejection in vivo). At higher concentrations (> 40 mu g/ml Hgb gamma) and equivalent concentrations of MPLA and GSH, the DCs induce populations of Treg which can suppress the induction of allogeneic CTL and graft rejection in vivo. These different populations of DCs express different patterns of mRNAs for the CD200R family. Addition of anti-TLR or anti-MD-1 mAbs to DCs developing in this mixture (Hgb gamma + GSH + MPLA), suggests that one effect of (GSH + Hgb gamma) on MPLA stimulation may involve altered signaling through TLR4. (c) 2009 Elsevier B.V. All rights reserved.