Dexamethasone selectively inhibits differentiation of cord blood stem cell derived-dendritic cell (DC) precursors into immature DCs.
Perinatal dexamethasone (Dx) alters the immune system leading to increased infections and developmental abnormalities. Dendritic cells (DCs) derived from cord-blood monocytes are especially Dx sensitive and we sought to determine the effects of Dx on cord-blood CD34+-DCs. Distinct stages of cord-blood CD34+-DC development were delineated: pre-DC, immature, and mature DCs. Dx added during development of pre-DCs did not suppress precursor number, or translocate the glucocorticoid receptor (GcR) from the cytoplasm to the nucleus. However, Dx added during pre-DCs differentiation into immature DCs, prompted GcR translocation to the nucleus, enhanced DC apoptosis, suppressed differentiation to CD1a+ cells, inhibited expression of CD86, reduced subsequent CD83 expression, maintained DC endocytic activity, suppressed IL-6 secretion, enhanced IL-10 secretion, and reduced DC-mediated T cell stimulation. Dx added during the maturation stage caused less dramatic effects. Thus, Dx stalled maturation, selectively induced apoptosis of developing DCs and the sensitivity peaked during pre-DCs differentiation into immature DCs.
Mainali
Elsie S
ES
Department of Pediatrics, Virginia Commonwealth University Health System, 401 North 12th Street, Room 6-500, Richmond, VA 23298, USA. emainali@hsc.vcu.edu
Tew
John G
JG
D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology*; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology; D006801:Humans; D010641:Phenotype; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000502:physiology
D018952:Antigens, CD34; D016207:Cytokines; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone