Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin

Tang, Aimin; Amagai, Masayuki; Granger, Laure; Stanley, John R.; Udey, Mark C.

doi:10.1038/361082a0

Cited by 446 publications

(308 citation statements)

References 24 publications

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“…These cytokines may mobilize LC from the epidermis by abolishing the E-cadherinmediated adhesion between LC and KC [71,72]. E-cadherin expression was down-regulated in a subpopulation of LC activated by in situ exposure to contact allergens, and by cutaneous administration of proinflammatory cytokines, including TNF-␣, IL-1␣, and IL-1␤.…”

Section: Proinflammatory Cytokines Stimulate Lc Migrationmentioning

confidence: 98%

Role of cytokines in epidermal Langerhans cell migration

Wang

Amerio

Sauder

1999

Journal of Leukocyte Biology

151

107

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Section: Proinflammatory Cytokines Stimulate Lc Migrationmentioning

confidence: 98%

Role of cytokines in epidermal Langerhans cell migration

Wang

Amerio

Sauder

1999

Journal of Leukocyte Biology

151

107

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“…They express the common DC marker CD1a but can be distinguished from other DC by the presence of intracellular Birbeck granules, containing the C-type lectin Langerin (CD207) (1), and by their expression of E-cadherin, enabling tight interaction with epithelial cells (2). LC are long-lived in comparison to other DC subtypes, and recent studies have highlighted the ability of LCprecursors to proliferate in situ (3).…”

Section: Angerhans Cells (Lc)mentioning

confidence: 99%

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Barbaroux

Beleut

Brisken

et al. 2008

The Journal of Immunology

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Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-κB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34+ progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 ± 1% vs 55.2 ± 5.7% live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 ± 77.2 vs 873.6 ± 41.6 LC per mm2; n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.

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“…Epidermal cells were prepared as described previously with slight modifications (27). Briefly, ears were split into dorsal and ventral halves and incubated in HBSS containing 0.5% trypsin and 1 mM EDTA for 45 min at 37°C.…”

Section: Preparation Of Cell Suspensions For Flow Cytometrymentioning

confidence: 99%

Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions

Nagao

Ginhoux

Leitner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

203

216

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A new langerin ؉ DC subset has recently been identified in murine dermis (langerin ؉ dDC), but the lineage and functional relationships between these cells and langerin ؉ epidermal Langerhans cells (LC) are incompletely characterized. Selective expression of the cell adhesion molecule EpCAM by LC allowed viable LC to be easily distinguished from langerin ؉ dDC in skin and lymphoid tissue and ex vivo as well. Differential expression of EpCAM and langerin revealed the presence of at least 3 distinct skin DC subsets. We determined that LC and langerin ؉ dDC exhibit different migratory capabilities in vitro and repopulate distinct anatomic compartments in skin at different rates after conditional depletion in vivo. Langerin ؉ dDC, in contrast to LC, did not require TGF␤1 for development. Carefully timed gene gun immunization studies designed to take advantage of the distinct repopulation kinetics of langerin ؉ dDC and LC revealed that langerin ؉ dDC were required for optimal production of ␤-galactosidase-specific IgG2a/c and IgG2b in the acute phase. In contrast, immunization via LC-deficient skin resulted in persistent and strikingly reduced IgG1 and enhanced IgG2a Ab production. Our data support the concepts that LC and langerin ؉ dDC represent distinct DC subsets that have specialized functions and that LC are important immunoregulatory cells. The presence of at least 3 functionally distinct skin DC subsets may have particular relevance for vaccines that are administered epicutaneously.EpCAM ͉ gene gun ͉ langerin ͉ TGF-beta T he remarkable phenotypic heterogeneity of DC, both between and within certain tissues, has been long recognized. To date, however, it has been possible to clearly relate DC phenotype to DC function in only a few instances, even in mice. For example, plasmacytoid DC are recognized as the primary source of virus-induced type I IFN (1), CD8␣ ϩ lymph node DC are largely responsible for cross-presentation of cell-associated antigen to CD8 T cells (2-4), and 33D1-reactive (DCIR2 ϩ ) splenic DC (as compared with CD205 ϩ DC) preferentially stimulate CD4 T cells (5). Epidermal Langerhans cells (LC) represent perhaps the most striking example of an extensively studied tissue DC subpopulation whose function is incompletely understood.LC have long been thought to play pivotal roles in initiating immunity by acquiring antigens that are encountered in skin, migrating to draining LN after activation, and stimulating antigen-specific T cells (6). However, recent studies suggested that LC do not function as essential antigen-presenting cells for anti-viral immune responses (2, 7) or for contact hypersensitivity reactions (8-12) in established murine models. Studies of LC have been challenging, in part, because readily detectable cell surface proteins that are constitutively expressed by epidermal LC and LC that have emigrated from epidermis have not been well recognized. The C-type lectin langerin has been regarded as a pathognomonic LC marker, but recent studies suggest that this protein is present in at le...

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Adhesion of epidermal Langerhans cells to keratinocytes mediated by E-cadherin

Cited by 446 publications

References 24 publications

Role of cytokines in epidermal Langerhans cell migration

Role of cytokines in epidermal Langerhans cell migration

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions

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