UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Cell-intrinsic regulation of murine dendritic cell function and survival by prereceptor amplification of glucocorticoid.
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Journal Article
  • Authors:
    Soulier A, Blois SM, Sivakumaran S, Fallah-Arani F, Henderson S, Flutter B, Rabbitt EH, Stewart PM, Lavery GG, Bennett C, Curnow SJ, Chakraverty R
  • Publication date:
    07/11/2013
  • Pagination:
    3288, 3297
  • Journal:
    Blood
  • Volume:
    122
  • Issue:
    19
  • Status:
    Published
  • Country:
    United States
  • PII:
    S0006-4971(20)36384-9
  • Language:
    eng
  • Keywords:
    11-beta-Hydroxysteroid Dehydrogenase Type 1, Animals, Apoptosis, Bone Marrow Transplantation, CD8 Antigens, Carbohydrate Dehydrogenases, Cells, Cultured, Corticosterone, Cyclopropanes, Dendritic Cells, Female, Gene Expression Regulation, Guanosine, Interferon Type I, Mice, Mice, Knockout, Receptors, Glucocorticoid, Signal Transduction, T-Lymphocytes, Toll-Like Receptors, Whole-Body Irradiation
Abstract
Although the inhibitory effects of therapeutic glucocorticoids (GCs) on dendritic cells (DCs) are well established, the roles of endogenous GCs in DC homeostasis are less clear. A critical element regulating endogenous GC concentrations involves local conversion of inactive substrates to active 11-hydroxyglucocorticoids, a reduction reaction catalyzed within the endoplasmic reticulum by an enzyme complex containing 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and hexose-6-phosphate dehydrogenase (H6PDH). In this study, we found that this GC amplification pathway operates both constitutively and maximally in steady state murine DC populations and is unaffected by additional inflammatory stimuli. Under physiologic conditions, 11βHSD1-H6PDH increases the sensitivity of plasmacytoid DCs (pDCs) to GC-induced apoptosis and restricts the survival of this population through a cell-intrinsic mechanism. Upon CpG activation, the effects of enzyme activity are overridden, with pDCs becoming resistant to GCs and fully competent to release type I interferon. CD8α(+) DCs are also highly proficient in amplifying GC levels, leading to impaired maturation following toll-like receptor-mediated signaling. Indeed, pharmacologic inhibition of 11βHSD1 synergized with CpG to enhance specific T-cell responses following vaccination targeted to CD8α(+) DCs. In conclusion, amplification of endogenous GCs is a critical cell-autonomous mechanism for regulating the survival and functions of DCs in vivo.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers
Author
Research Department of Haematology
Author
Research Department of Cancer Bio
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by