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Blood, 15 September 2001, Vol. 98, No. 6, pp. 1987-1988
CORRESPONDENCE
To the editor:
Langerhans cells and the cells of Langerhans cell histiocytosis
do not express DC-SIGN
Geissmann and colleagues recently reported that cells of
Langerhans cell histiocytosis (LCH) in osseous and/or chronic lesions have an immature dendritic cell phenotype.1 In addition to CD1a, LCH cells in all 25 cases examined expressed Langerin, a recently
described C-type lectin that appears to be restricted entirely to
Langerhans cells.2 An increasing number of dendritic cell lectins, such as dendritic
cell-specific ICAM-grabbing nonintegrin (DC-SIGN), dendritic cell immunoreceptor (DCIR), DEC-205, and CD23, are now
recognized.3 We consider it important to determine whether
these lectins are expressed on similar, overlapping, or mutually
exclusive dendritic cell subsets, as such information may suggest the
biological roles of the individual lectins. Our recent work has focused
on DC-SIGN (manuscript submitted and Soilleux et
al4), which has 32% sequence identity at the
amino acid level to Langerin across the carbohydrate recognition
domain. DC-SIGN has the capacity to bind the HIV surface molecule
glycoprotein 120 in an inhibitable manner by
mannose,5,6 as well as the lymphocytic surface-expressed
molecule ICAM-3,7 and the endothelial surface molecule
ICAM-2.8 Langerin also possesses the critical mannose
binding motif seen in DC-SIGN. It has not yet been determined whether
HIV may interact with Langerin in a manner analogous to its interaction
with DC-SIGN. We have recently demonstrated that DC-SIGN is expressed by cells with
an immature dendritic cell phenotype (manuscript submitted) similar to
that described by Geissmann et al1 in LCH cells. In
our study, the DC-SIGN+ cells were CD14low
HLA-DR+/low CD68+
8100+/ and only rarely expressed dendritic cell
activation markers such as CD83, CD86, and cmrf-44 (manuscript
submitted). Moreover, the DC-SIGN+ cells were consistently
negative for CDla (manuscript submitted). Cells matured in the
presence of granulocyte-macrophage colony-stimulating factor (GM-CSF),
tumor necrosis factor- (TNF-), transforming growth factor  (TGF-), stem cell factor (SCF), and flt-3 ligand from
CD34+lin peripheral blood cell precursors, to
give a Langerhans cell phenotype,9 showed no evidence
of DC-SIGN expression by reverse transcriptase-polymerase chain
reaction (RT-PCR).4 Dendritic cells matured from
peripheral blood monocytes in the presence of GM-CSF and interleukin-4
(IL-4) and could be shown to express DC-SIGN both by RT-PCR and
fluorescence-activated cell sorting analysis (manuscript submitted and
Soilleux et al4). In view of the findings of Geissmann et al,1 we have
extended our analysis of the expression of DC-SIGN in relation to CDla
on dendritic cells by examining 4 specimens of normal skin and 8 specimens of LCH obtained from the Department of Histopathology, Addenbrooke's Hospital, Cambridge, United Kingdom. Two of the LCH
cases were from the retro-orbital region, 3 were from bone, and 1 was
from skin. We performed immunohistochemistry on serial sections using
our rabbit polyclonal anti-DC-SIGN antibody (manuscript submitted) and
mouse monoclonal anti-CDla (Novacastra, Newcastle-upon-Tyne, United Kingdom). In all 4 specimens of normal skin, the CD1a+ cells in the
epidermis and at the dermo-epidermal junction did not express DC-SIGN, whereas CDla dendritic cells present within the dermis
did (Figure 1A-B). In all 8 specimens of
LCH, the CDla+ cells within the infiltrate were negative
for DC-SIGN, though occasional DC-SIGN-expressing cells could be seen
in surrounding tissue acting as a useful internal positive control
(Figure 1C-D). Our data are in accordance with previous results
suggesting that expression of DC-SIGN and expression of the Langerhans
cell-restricted molecule CDla are mutually exclusive (manuscript
submitted, Soilleux et al,4 and Geijtenbeek et
al7). Our findings, when considered with those of
Geissmann et al, indicate that DC-SIGN is only expressed on a subset of
dendritic cells with an immature phenotype. Given the very similar
expression patterns of Langerin and CD1a,1 our data
suggest that DC-SIGN and Langerin are expressed by mutually exclusive
dendritic cell subsets. Whether there are functional differences
between Langerhans cells and DC-SIGN+ dendritic cells
remains to be determined. The 2 novel C-type lectins, Langerin and
DC-SIGN, may have analogous properties on separate dendritic cell
subsets with respect to, for example, their capacity to bind T
lymphocytes and lentiviruses.
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| Figure 1.
DC-SIGN and Langerhans cell histiocyosis.
(A) Normal skin shows positive immunostaining for CDla on
dendritic cells within the epidermis and at the dermo-epidermal
junction. (B) Serial section of skin from panel A shows positive
immunostaining for DC-SIGN on cells within the dermis only. No
epidermal dendritic cells express DC-SIGN. (C) Langerhans cell
histiocyosis from the retro-orbital region showing immunostaining for
CDla on numerous large cells. (D) DC-SIGN staining of a serial section
of the specimen in panel C shows no expression of DC-SIGN on these
large CDla+ cells. Sections were immunostained using the
peroxidase technique and counterstained with hematoxylin. Sections were
photographed at × 100.
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Elizabeth J. Soilleux and Nicholas Coleman
Correspondence: Elizabeth J. Soilleux, Department of
Molecular Histopathology, Addenbrooke's Hospital, Hills Road,
Cambridge, CB2 2QQ United Kingdom; e-mail: ejs17{at}cam.ac.uk
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