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Blood, 15 December 2000, Vol. 96, No. 13, pp. 4276-4284
IMMUNOBIOLOGY
Ligation of E-cadherin on in vitro-generated immature
Langerhans-type dendritic cells inhibits their maturation
Elisabeth Riedl,
Johannes Stöckl,
Otto Majdic,
Clemens Scheinecker,
Walter Knapp, and
Herbert Strobl
From the Vienna International Research Cooperation
Center/Novartis Research Institute and the Departments of Dermatology I
and Internal Medicine III, Institute of Immunology, University of
Vienna, Vienna, Austria.
Epithelial tissues of various organs contain immature Langerhans
cell (LC)-type dendritic cells, which play key roles in immunity. LCs
reside for long time periods at an immature stage in epithelia before
migrating to T-cell-rich areas of regional lymph nodes to become
mature interdigitating dendritic cells (DCs). LCs express the
epithelial adhesion molecule E-cadherin and undergo homophilic E-cadherin adhesion with surrounding epithelial cells. Using a defined
serum-free differentiation model of human CD34+
hematopoietic progenitor cells, it was demonstrated that LCs generated
in vitro in the presence of transforming growth factor  1 (TGF-1)
express high levels of E-cadherin and form large homotypic cell
clusters. Homotypic LC clustering can be inhibited by the addition of
anti-E- cadherin monoclonal antibodies (mAbs). Loss of E-cadherin
adhesion of LCs by mechanical cluster disaggregation correlates with
the rapid up-regulation of CD86, neo-expression of CD83, and diminished
CD1a cell surface expression by LCs specific phenotypic features of
mature DCs. Antibody ligation of E-cadherin on the surfaces of immature
LCs after mechanical cluster disruption strongly reduces the
percentages of mature DCs. The addition of mAbs to the adhesion
molecules LFA-1 or CD31 to parallel cultures similarly inhibits
homotypic LC cluster formation, but, in contrast to anti-E-cadherin,
these mAbs fail to inhibit DC maturation. Thus, E-cadherin engagement
on immature LCs specifically inhibits the acquisition of mature DC
features. E-cadherin-mediated LC maturation suppression may represent
a constitutive active epithelial mechanism that prevents the
uncontrolled maturation of immature LCs.
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