Induction of regulatory dendritic cells by dexamethasone and 1alpha,25-Dihydroxyvitamin D(3).
Dendritic cells (DC) modulated to induce T cell hyporesponsiveness have promising potential in immunotherapy of autoimmune disorders and for the prevention of allograft rejection. While studying the effect of immunosuppressive agents on the maturation of DC we found that 1alpha,25-Dihydroxyvitamin D(3) the active form of Vitamin D(3) (D(3)) in combination with dexamethasone (Dex) has a synergistic effect on LPS-induced maturation of DC. Monocyte-derived DCs cultured with D(3) and Dex during LPS-induced maturation have a low stimulatory effect on allogeneic T cells comparable with that of immature DCs. But in contrast to immature DCs, D3/Dex exposed DCs secrete IL-10 and show upregulated transcription of mRNA encoding the Ig-like inhibitory receptor ILT4. D3/Dex exposed DCs also inhibit alloreactivity and slightly enhance the degree of apoptosis in mature DCs. Thus, D(3)/Dex is an effective immunosuppressive drug combination for the induction of DCs capable of inducing T cell hyporesponsiveness.
Pedersen
Anders Elm
AE
Department of Medical Anatomy A, The Panum Institute, University of Copenhagen, Copenhagen, Denmark. elmpedersen@mai.ku.dk
Gad
Monika
M
Walter
Mark R
MR
Claesson
Mogens Helweg
MH
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D002120:Calcium Channel Agonists; C491341:LILRB2 protein, human; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D016753:Interleukin-10; D003907:Dexamethasone; D002117:Calcitriol