M3i

@article{camara_lymph_2019,

title = {Lymph Node Mesenchymal and Endothelial Stromal Cells Cooperate via the RANK-RANKL Cytokine Axis to Shape the Sinusoidal Macrophage Niche},

author = {Abdouramane Camara and Olga G Cordeiro and Farouk Alloush and Janina Sponsel and Mélanie Chypre and Lucas Onder and Kenichi Asano and Masato Tanaka and Hideo Yagita and Burkhard Ludewig and Vincent Flacher and Christopher G Mueller},

doi = {10.1016/j.immuni.2019.05.008},

issn = {1097-4180},

year  = {2019},

date = {2019-01-01},

journal = {Immunity},

volume = {50},

number = {6},

pages = {1467--1481.e6},

abstract = {Tissue-resident macrophages are receptive to specific signals concentrated in cellular niches that direct their cell differentiation and maintenance genetic programs. Here, we found that deficiency of the cytokine RANKL in lymphoid tissue organizers and marginal reticular stromal cells of lymph nodes resulted in the loss of the CD169+ sinusoidal macrophages (SMs) comprising the subcapsular and the medullary subtypes. Subcapsular SM differentiation was impaired in mice with targeted RANK deficiency in SMs. Temporally controlled RANK removal in lymphatic endothelial cells (LECs) revealed that lymphatic RANK activation during embryogenesis and shortly after birth was required for the differentiation of both SM subtypes. Moreover, RANK expression by LECs was necessary for SM restoration after inflammation-induced cell loss. Thus, cooperation between mesenchymal cells and LECs shapes a niche environment that supports SM differentiation and reconstitution after inflammation.},

keywords = {Activation, Animals, Biomarkers, Cell Differentiation, Cells, Cellular, Cellular Microenvironment, cytokine, Cytokines, deficiency, Differentiation, Endothelial Cells, ENDOTHELIAL-CELLS, environment, Expression, immune regulation, Immunology, Immunophenotyping, inflammation, LYMPH, LYMPH NODE, Lymph Nodes, lymphatic endothelial cells, Lymphoid Tissue, Macrophage, Macrophages, Mesenchymal Stem Cells, mesenchymal stromal cells, Mice, rank, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Stromal Cells, Team-Mueller, transgenic},

pubstate = {published},

tppubtype = {article}

}

@article{chypre_porphyrin_2017,

title = {Porphyrin Derivatives Inhibit the Interaction between Receptor Activator of NF-κB and Its Ligand},

author = {Mélanie Chypre and Maria-Bernadette Madel and Olivier Chaloin and Claudine Blin-Wakkach and Christophe Morice and Christopher G Mueller},

doi = {10.1002/cmdc.201700462},

issn = {1860-7187},

year  = {2017},

date = {2017-10-01},

journal = {ChemMedChem},

volume = {12},

number = {20},

pages = {1697--1702},

abstract = {Receptor activator of NF-κB (RANK), a member of the TNF-receptor superfamily, plays an important role in bone resorption and stimulates immune and epithelial cell activation. Denosumab, a human monoclonal antibody that blocks the RANK ligand (RANKL), is approved for the treatment of osteoporosis and bone metastasis. However, a small molecule that inhibits the RANK-RANKL interaction would be beneficial to decrease cost and to facilitate treatments with orally available therapeutic agents. Herein we report the discovery of the first nonpeptidic inhibitors of RANK-RANKL interactions. In screening a chemical library by competitive ELISA, the porphyrin verteporfin was identified as a hit. Derivatives were screened, and the chlorin-macrocycle-containing pheophorbide A and purpurin 18 were found to bind recombinant RANKL, to inhibit RANK-RANKL interactions in the ELISA, and to suppress the RANKL-dependent activation of model cells and the differentiation of RANK-expressing precursors into osteoclasts. This discovery of a family of small molecules that inhibit RANK activation presents an initial basis for further development of nonpeptidic therapeutic agents targeting the interaction between RANK and RANKL.},

keywords = {Animals, Cell Survival, cell-based assays, ELISA, Humans, Jurkat Cells, Mice, Molecular Structure, Osteoclasts, Osteogenesis, porphyrins, Protein Binding, RANK ligand, receptor activator of NF-κB, Receptor Activator of Nuclear Factor-kappa B, Structure-Activity Relationship, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{onder_lymphatic_2017,

title = {Lymphatic Endothelial Cells Control Initiation of Lymph Node Organogenesis},

author = {Lucas Onder and Urs Mörbe and Natalia Pikor and Mario Novkovic and Hung-Wei Cheng and Thomas Hehlgans and Klaus Pfeffer and Burkhard Becher and Ari Waisman and Thomas Rülicke and Jennifer Gommerman and Christopher G Mueller and Shinichiro Sawa and Elke Scandella and Burkhard Ludewig},

doi = {10.1016/j.immuni.2017.05.008},

issn = {1097-4180},

year  = {2017},

date = {2017-07-01},

journal = {Immunity},

volume = {47},

number = {1},

pages = {80--92.e4},

abstract = {Lymph nodes (LNs) are strategically situated throughout the body at junctures of the blood vascular and lymphatic systems to direct immune responses against antigens draining from peripheral tissues. The current paradigm describes LN development as a programmed process that is governed through the interaction between mesenchymal lymphoid tissue organizer (LTo) cells and hematopoietic lymphoid tissue inducer (LTi) cells. Using cell-type-specific ablation of key molecules involved in lymphoid organogenesis, we found that initiation of LN development is dependent on LTi-cell-mediated activation of lymphatic endothelial cells (LECs) and that engagement of mesenchymal stromal cells is a succeeding event. LEC activation was mediated mainly by signaling through receptor activator of NF-κB (RANK) and the non-canonical NF-κB pathway and was steered by sphingosine-1-phosphate-receptor-dependent retention of LTi cells in the LN anlage. Finally, the finding that pharmacologically enforced interaction between LTi cells and LECs promotes ectopic LN formation underscores the central LTo function of LECs.},

keywords = {Animals, Cell Differentiation, Cells, Choristoma, Cultured, Embryo, Endothelial Cells, fibroblastic reticular cells, Inbred C57BL, lymph node organogenesis, Lymph Nodes, lymphatic and blood endothelial cells, lymphoid stromal cells, lymphoid tissue organizer cells, Lymphotoxin beta Receptor, Lysosphingolipid, Mammalian, Mesenchymal Stem Cells, mesenchymal stromal cells, Mice, NF-kappa B, Organogenesis, Receptor Activator of Nuclear Factor-kappa B, Receptors, Signal Transduction, Team-Mueller, transgenic},

pubstate = {published},

tppubtype = {article}

}

@article{chypre_characterization_2016,

title = {Characterization and application of two RANK-specific antibodies with different biological activities},

author = {M Chypre and J Seaman and O G Cordeiro and L Willen and K A Knoop and A Buchanan and R C Sainson and I R Williams and H Yagita and P Schneider and C G Mueller},

doi = {10.1016/j.imlet.2016.01.003},

year  = {2016},

date = {2016-03-01},

journal = {Immunol.Lett.},

volume = {171},

number = {1879-0542 (Electronic)},

pages = {5--14},

abstract = {Antibodies play an important role in therapy and investigative biomedical research. The TNF-family member Receptor Activator of NF-kappaB (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-kappaB 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},

keywords = {Activation, Animals, ANTAGONIST, Antibodies, antibody, Antibody Affinity, Apoptosis, Assay, Cell Differentiation, Cell Surface Display Techniques, Cellular, Chemistry, comparison, Dendritic Cells, DERMAL DENDRITIC CELLS, Epithelial Cells, Epithelial microfold cell, Epitopes, Fusion, FUSION PROTEIN, HEK293 Cells, Homeostasis, Human, Humans, immune regulation, Immunization, Immunology, Immunomodulation, immunopathology, In vivo, Inbred C57BL, Intestines, Jurkat Cells, Langerhans cell, Langerhans Cells, Mice, Monoclonal, monoclonal antibody, MONOCLONAL-ANTIBODY, mouse, NF-kappa B, NF-kappaB, pathology, Protein, rank, RANK (TNFRSF11a), Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Secondary, Signal Transduction, signaling, Team-Mueller, therapy},

pubstate = {published},

tppubtype = {article}

}

@article{duheron_receptor_2011,

title = {Receptor activator of NF-kappaB (RANK) stimulates the proliferation of epithelial cells of the epidermo-pilosebaceous unit},

author = {V Duheron and E Hess and M Duval and M Decossas and B Castaneda and J E Klopper and L Amoasii and J B Barbaroux and I R Williams and H Yagita and J Penninger and Y Choi and F Lezot and R Groves and R Paus and C G Mueller},

doi = {10.1073/pnas.1013054108},

year  = {2011},

date = {2011-03-01},

journal = {Proc.Natl.Acad.Sci.U.S.A},

volume = {108},

number = {1091-6490 (Electronic)},

pages = {5342--5347},

abstract = {Receptor activator of NF-kappaB (RANK), known for controlling bone mass, has been recognized for its role in epithelial cell activation of the mammary gland. Because bone and the epidermo-pilosebaceous unit of the skin share a lifelong renewal activity where similar molecular players operate, and because mammary glands and hair follicles are both skin appendages, we have addressed the function of RANK in the hair follicle and the epidermis. Here, we show that mice deficient in RANK ligand (RANKL) are unable to initiate a new growth phase of the hair cycle and display arrested epidermal homeostasis. However, transgenic mice overexpressing RANK in the hair follicle or administration of recombinant RANKL both activate the hair cycle and epidermal growth. RANK is expressed by the hair follicle germ and bulge stem cells and the epidermal basal cells, cell types implicated in the renewal of the epidermo-pilosebaceous unit. RANK signaling is dispensable for the formation of the stem cell compartment and the inductive hair follicle mesenchyme, and the hair cycle can be rescued by Rankl knockout skin transplantation onto nude mice. RANKL is actively transcribed by the hair follicle at initiation of its growth phase, providing a mechanism for stem cell RANK engagement and hair-cycle entry. Thus, RANK-RANKL regulates hair renewal and epidermal homeostasis and provides a link between these two activities},

keywords = {Activation, Animals, Cell Proliferation, Chemistry, cytology, Epidermis, Epithelial Cells, function, Genetics, Growth, Hair, hair follicle, Homeostasis, Immunology, Inbred C57BL, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, Nude, Osteoprotegerin, physiology, Proliferation, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, signaling, Skin, Skin Transplantation, stem, Stem Cells, Team-Mueller, transgenic, TRANSGENIC MICE, TRANSPLANTATION},

pubstate = {published},

tppubtype = {article}

}

@article{barbaroux_epidermal_2008,

title = {Epidermal receptor activator of NF-kappaB ligand controls Langerhans cells numbers and proliferation},

author = {J B Barbaroux and M Beleut and C Brisken and C G Mueller and R W Groves},

year  = {2008},

date = {2008-01-01},

journal = {Journal of Immunology},

volume = {181},

number = {1550-6606 (Electronic)},

pages = {1103--1108},

abstract = {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-kappaB 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 textless 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 mm(2); n = 9; p textless 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},

keywords = {APC, Apoptosis, BLOOD, Cell Count, Cell Proliferation, Cell Survival, Culture, cytology, Dendritic Cells, DERMATOLOGY, Differentiation, Epidermis, Expression, Homeostasis, Human, Humans, Immunology, IN VITRO, In vivo, KERATINOCYTES, Langerhans Cells, ligand, metabolism, Mice, NF-kappa B, NF-kappaB, OSTEOCLAST, Osteoclasts, Proliferation, Protein, rank, RANK ligand, Receptor, Receptor Activator of Nuclear Factor-kappa B, Regulation, Signal Transduction, Skin, survival, Team-Mueller, viability},

pubstate = {published},

tppubtype = {article}

}

@article{barbaroux_tumor_2006,

title = {Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors},

author = {Jean-Baptiste Barbaroux and Wing-Hong Kwan and Jean-Pierre Allam and Natalija Novak and Thomas Bieber and Wolf H Fridman and Richard Groves and Chris G Mueller},

doi = {10.1038/sj.jid.5700023},

issn = {0022-202X},

year  = {2006},

date = {2006-01-01},

journal = {The Journal of Investigative Dermatology},

volume = {126},

number = {1},

pages = {114--120},

abstract = {GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.},

keywords = {Antigens, C-Type, Carrier Proteins, CC, CCR6, CD, CD1, CD34, Cell Differentiation, Chemokine, Chemokine CCL20, chemokines, Cytokines, DERMIS, FRANZ, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, IL-4, Interleukin-4, Langerhans Cells, Lectins, Lipopolysaccharide Receptors, M-CSF, Macrophage Colony-Stimulating Factor, Macrophage Inflammatory Proteins, Mannose-Binding Lectins, Membrane Glycoproteins, murine, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Surface, Team-Mueller, TNF ALPHA, Tumor Necrosis Factor-alpha},

pubstate = {published},

tppubtype = {article}

}