Journal of Leukocyte Biology eBioscience full spectrum cell analysis
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published online as doi:10.1189/jlb.1107792 on March 11, 2008

Published online before print March 11, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jlb.1107792v1
83/6/1476    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Varas, A.
Right arrow Articles by Vicente, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Varas, A.
Right arrow Articles by Vicente, A.
(Journal of Leukocyte Biology. 2008;83:1476-1483.)
© 2008 by Society for Leukocyte Biology

Survival and function of human thymic dendritic cells are dependent on autocrine Hedgehog signaling

Alberto Varas*,1, Carmen Hernández-López*, Jaris Valencia*, Silvia Mattavelli{dagger}, Victor G. Martínez*, Laura Hidalgo*, Cruz Gutiérrez-Frías*, Agustín G. Zapata{dagger}, Rosa Sacedón* and Angeles Vicente*

* Department of Cell Biology, Faculties of Medicine and
{dagger} Biology, Complutense University, Madrid, Spain

1Correspondence: Department of Cell Biology, Faculty of Medicine, Avda. Complutense s/n, Ciudad Universitaria, Complutense University, 28040 Madrid, Spain. E-mail: avaras{at}bio.ucm.es

The Hedgehog (Hh) family of signaling molecules functions in the development of numerous tissues during embryogenesis and has also been involved in adult self-renewing tissues. Recent results have demonstrated that the different components of the Hh signaling pathway are expressed in the human thymus. In this study, we investigate whether thymic dendritic cells (DCs) are cell targets for Hh signaling. Both components of the Hh receptor, Patched and Smoothened, as well as other Hh-binding proteins with modulating functions, are expressed by human thymic DCs. The expression of Gli1, Gli2, and Gli3 transcription factors suggests that the Hh signaling pathway is active in thymic DCs, and approximately one-half of thymic DCs produces Sonic Hh (Shh). The culture of thymic DCs with Shh protects them from apoptosis [similarly to CD40 ligand (CD40L)], and these antiapoptotic effects are related to an up-regulation of Bcl-2 and Bcl-XL protein expression. The addition of the Hh pathway inhibitor, cyclopamine, decreases DC viability and impairs their allostimulatory function in vitro. In addition, the blockade of the Hh signaling pathway by cyclopamine treatment abrogates the up-regulation of HLA-DR, CD86, CD80, and CD83 expression induced by CD40L on thymic DCs. Finally, we also show that after activation with CD40L thymic DCs down-regulate the expression of Hh receptor components as well as Shh production. Taken together, these results suggest that the survival and function of thymic DCs are regulated by an autocrine Hh signaling.

Key Words: thymus • cyclopamine • Patched • Smoothened






HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the Society for Leukocyte Biology.