Langerhans cell precursors acquire RANK/CD265 in prenatal human skin

Schöppl, Alice; Botta, Albert; Prior, Marion; Akgün, Johnnie; Schuster, Christopher; Elbe‐Bürger, Adelheid

doi:10.1016/j.acthis.2015.01.003

Cited by 8 publications

(6 citation statements)

References 26 publications

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“…In healthy adult human epidermis, flow cytometry reveals that ~95% of LCs express RANK ( 86 ), while keratinocytes express low levels of RANKL. LC gradually acquire RANK during gestation, reaching levels comparable with adult skin in the third trimester of pregnancy—a phenomenon previously observed for other markers on LCs in prenatal human skin ( 87 ).…”

Section: Nf-κb Systemsupporting

confidence: 71%

“…A similar signaling cascade seems to be activated in the immunosuppressive context that results from ultraviolet irradiation. Keratinocytes upregulate RANKL and trigger RANK expressing LCs ( 88 ) preferentially to expand the subset of CD4 + CD25 + Treg suppressive for local and systemic immune reactions ( 87 ). Furthermore, LCs stimulated with sRANKL have been shown to augment the expression of C–C motif chemokine ligand 17 (CCL17), and induce Foxp3 + Tregs ( 89 ).…”

Section: Nf-κb Systemmentioning

confidence: 99%

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Langerhans Cells—Programmed by the Epidermis

et al. 2017

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Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, “non-dangerous” situation, LCs coordinate a continuous state of immune tolerance, preventing unnecessary and harmful immune activation. Conversely, when they sense a danger signal, for example during infection or when the physical integrity of skin has been compromised as a result of a trauma, they instruct T lymphocytes of the adaptive immune system to mount efficient effector responses. Recent advances investigating the molecular mechanisms underpinning the cross talk between LCs and the epidermal microenvironment reveal its importance for programming LC biology. This review summarizes the novel findings describing LC origin and function through the analysis of the transcriptomic programs and gene regulatory networks (GRNs). Review and meta-analysis of publicly available datasets clearly delineates LCs as distinct from both conventional dendritic cells (DCs) and macrophages, suggesting a primary role for the epidermal microenvironment in programming LC biology. This concept is further supported by the analysis of the effect of epidermal pro-inflammatory signals, regulating key GRNs in human and murine LCs. Applying whole transcriptome analyses and in silico analysis has advanced our understanding of how LCs receive, integrate, and process signals from the steady-state and diseased epidermis. Interestingly, in homeostasis and under immunological stress, the molecular network in LCs remains relatively stable, reflecting a key evolutionary need related to tissue localization. Importantly, to fulfill their key role in orchestrating antiviral adaptive immune responses, LC share specific transcriptomic modules with other DC types able to cross-present antigens to cytotoxic CD8+ T cells, pointing to a possible evolutionary convergence mechanism. With the development of more advanced technologies allowing delineation of the molecular networks at the level of chromatin organization, histone modifications, protein translation, and phosphorylation, future “omics” investigations will bring in-depth understanding of the complex molecular mechanisms underpinning human LC biology.

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Section: Nf-κb Systemsupporting

confidence: 71%

Section: Nf-κb Systemmentioning

confidence: 99%

Langerhans Cells—Programmed by the Epidermis

et al. 2017

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“…To investigate whether the antibodies are suitable for the detection of endogenous RANK, we incubated them with primary human skin dermal dendritic cells and Langerhans cells. Langerhans cells have previously been shown to express RANK using the mAb683 (R&D Systems) [18,19]. Whether the related dermal dendritic cells also express RANK is not known.…”

Section: Labelling Of Rank On Primary Human Langerhans Cells With Ranmentioning

confidence: 99%

“…Macrophages and dendritic cells are of the same lineage as osteoclasts and express this receptor. RANK activation of these cells enhances the immune response by increased cell survival and cytokine production [3,4,8,[15][16][17][18][19][20]. Also epithelial cells are responsive to RANKL.…”

Section: Introductionmentioning

confidence: 99%

Characterization and application of two RANK-specific antibodies with different biological activities

Chypre

Seaman²,

Cordeiro

et al. 2016

Immunology Letters

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Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-κB (RANK) is known for its role in bone homeostasis and is increasingly recognized as a central player in immune regulation and epithelial cell activation. However, the study of RANK biology has been hampered by missing or insufficient characterization of high affinity tools that recognize RANK. Here, we present a careful description and comparison of two antibodies, RANK-02 obtained by phage display (Newa, 2014 [1]) and R12-31 generated by immunization (Kamijo, 2006 [2]). We found that both antibodies recognized mouse RANK with high affinity, while RANK-02 and R12-31 recognized human RANK with high and lower affinities, respectively. Using a cell apoptosis assay based on stimulation of a RANK:Fas fusion protein, and a cellular NF-κB signaling assay, we showed that R12-31 was agonist for both species. R12-31 interfered little or not at all with the binding of RANKL to RANK, in contrast to RANK-02 that efficiently prevented this interaction. Depending on the assay and species, RANK-02 was either a weak agonist or a partial antagonist of RANK. Both antibodies recognized human Langerhans cells, previously shown to express RANK, while dermal dendritic cells were poorly labeled. In vivo R12-31 agonist activity was demonstrated by its ability to induce the formation of intestinal villous microfold cells in mice. This characterization of two monoclonal antibodies should now allow better evaluation of their application as therapeutic reagents and investigative tools.

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“…In the present special issue, our aim is to provide original and review articles dealing with the morphological features and the dynamic patterns of expression of several immunomarkers during human fetal development (Frausin et al, 2015;Giuffrè et al, 2015;Kraljevic et al, 2015;Magro et al, 2015a,b;Musumeci et al, 2015a,b,c;Parenti et al, 2015;Sanna et al, 2015;Schöppl et al, 2015) and in neoplastic tissues (Lopes et al, 2015;Magro et al, 2015a,b,c,d;Miskovic et al, 2015;Poljicanin et al, 2015;Salvatorelli et al, 2015). Notably, some of these markers (WT1 protein and cyclin D1) have been identified in some pediatric malignant tumors (neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma), recapitulating their developmental expression profile (Magro et al, 2015b,c,d;Parenti et al, 2015;Salvatorelli et al, 2015).…”

mentioning

confidence: 98%