Publications
2020
Brulefert Adrien, Hoste Astrid, Muller Quentin, Fauny Jean-Daniel, Mueller Christopher G, Flacher Vincent
Vitamin D3-elicited CD14+ human skin dendritic cells promote thymic stromal lymphopoietin-independent type 2 T-helper responses Article de journal
Dans: Allergy, 2020, ISSN: 1398-9995.
Résumé | Liens | BibTeX | Étiquettes: atopic dermatitis, Dendritic cell, T helper 2, Team-Mueller, thymic stromal lymphopoietin, vitamin D3
@article{brulefert_vitamin_2020,
title = {Vitamin D3-elicited CD14+ human skin dendritic cells promote thymic stromal lymphopoietin-independent type 2 T-helper responses},
author = {Adrien Brulefert and Astrid Hoste and Quentin Muller and Jean-Daniel Fauny and Christopher G Mueller and Vincent Flacher},
doi = {10.1111/all.14718},
issn = {1398-9995},
year = {2020},
date = {2020-01-01},
journal = {Allergy},
abstract = {BACKGROUND: Immune modulation by vitamin D3 through dendritic cells (DCs) remains controversial. Human DCs exposed in vitro counteract type-1 T-helper (Th1) differentiation and induce regulatory T cells. However, cutaneous application on mice promotes Th2-driven inflammation resembling atopic dermatitis and relying on thymic stromal lymphopoietin (TSLP) from keratinocytes and T-cell orientation by TSLP-stimulated skin DCs. We studied the effects of vitamin D3 in human skin, focusing on TSLP production and the role of skin DCs in T-cell differentiation.
METHODS: Human healthy skin explants were exposed in vitro to vitamin D3 analogs. Migrating DCs were analyzed and TSLP quantified in the supernatant. Allogeneic naïve CD4+ T cells were cocultured with DCs to assess their proliferation and cytokine production.
RESULTS: Vitamin D3 induced skin DCs to differentiate Th2 cells producing IL-4 and IL-13. Vitamin D3 triggered TSLP release in textasciitilde30% of skin explants, correlating with IL-13 detection in Th2 cells. In these donors, blocking TSLP receptor during skin explant cultures abrogated IL-13 production, yet IL-4+ Th2 cells were unaffected. Among skin DCs emerged CD14+ cells that had responded directly to vitamin D3 and differed from classical CD14+ dermal emigrants. Vitamin D3-elicited CD14+ DCs sufficed to promote IL-4+ Th2 cells in a TSLP-independent manner.
CONCLUSION: Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.},
keywords = {atopic dermatitis, Dendritic cell, T helper 2, Team-Mueller, thymic stromal lymphopoietin, vitamin D3},
pubstate = {published},
tppubtype = {article}
}
METHODS: Human healthy skin explants were exposed in vitro to vitamin D3 analogs. Migrating DCs were analyzed and TSLP quantified in the supernatant. Allogeneic naïve CD4+ T cells were cocultured with DCs to assess their proliferation and cytokine production.
RESULTS: Vitamin D3 induced skin DCs to differentiate Th2 cells producing IL-4 and IL-13. Vitamin D3 triggered TSLP release in textasciitilde30% of skin explants, correlating with IL-13 detection in Th2 cells. In these donors, blocking TSLP receptor during skin explant cultures abrogated IL-13 production, yet IL-4+ Th2 cells were unaffected. Among skin DCs emerged CD14+ cells that had responded directly to vitamin D3 and differed from classical CD14+ dermal emigrants. Vitamin D3-elicited CD14+ DCs sufficed to promote IL-4+ Th2 cells in a TSLP-independent manner.
CONCLUSION: Vitamin D3, despite inducing TSLP in some donors, had a direct influence on skin DCs, affecting their phenotype and ability to drive Th2 responses independently of TSLP. Our findings pave the way toward in vitro systems that accurately model human cutaneous Th2 responses, notably involved in atopic dermatitis.
2019
Mueller Christopher G, Voisin Benjamin
Of skin and bone: did Langerhans cells and osteoclasts evolve from a common ancestor? Article de journal
Dans: Journal of Anatomy, vol. 235, no. 2, p. 412–417, 2019, ISSN: 1469-7580.
Résumé | Liens | BibTeX | Étiquettes: Animals, Biological Evolution, Dendritic cell, Evolution, hair follicle, Humans, Langerhans cell, Langerhans Cells, Macrophage, OSTEOCLAST, Osteoclasts, Team-Mueller
@article{mueller_skin_2019,
title = {Of skin and bone: did Langerhans cells and osteoclasts evolve from a common ancestor?},
author = {Christopher G Mueller and Benjamin Voisin},
doi = {10.1111/joa.12543},
issn = {1469-7580},
year = {2019},
date = {2019-08-01},
journal = {Journal of Anatomy},
volume = {235},
number = {2},
pages = {412--417},
abstract = {Skin Langerhans cells are antigen-presenting cells of the interfollicular epidermis and the upper part of the hair follicle, whereas osteoclasts are specialized bone-resorbing macrophages. Although at first view these two cell types appear to have little in common, a closer analysis reveals shared features, and when taking into account their surrounding environment, a hypothesis can be developed that Langerhans cells and osteoclasts have evolved from a common ancestral cell type. In this mini-review, we have compared the ontogenetic features of Langerhans cells and osteoclasts from a genetic and a functional point of view, an issue that so far has been overlooked. The gene programs that control cell differentiation, and the body parts where they reside, present surprising similarities. Whereas the function of osteoclasts in bone degradation has been established since the first vertebrates, Langerhans cells may have undergone a stepwise adaptation from aquatic to terrestrial life. Their cell function co-evolved with the imperatives of the skin to protect against physical impact, heat, water loss and pathogens, which implied the capacity of Langerhans cells to associate with skin appendages and to develop immunostimulatory functions. For the highly versatile and efficient immune system of modern vertebrates, Langerhans cells may be a memory of the past.},
keywords = {Animals, Biological Evolution, Dendritic cell, Evolution, hair follicle, Humans, Langerhans cell, Langerhans Cells, Macrophage, OSTEOCLAST, Osteoclasts, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}
Schaeffer Evelyne, Sánchez-Fernández Elena M, Gonçalves-Pereira Rita, Flacher Vincent, Lamon Delphine, Duval Monique, Fauny Jean-Daniel, Fernández José M García, Mueller Christopher G, Mellet Carmen Ortiz
sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo Article de journal
Dans: European Journal of Medicinal Chemistry, vol. 169, p. 111–120, 2019, ISSN: 1768-3254.
Résumé | Liens | BibTeX | Étiquettes: Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller
@article{schaeffer_sp2-iminosugar_2019,
title = {sp2-Iminosugar glycolipids as inhibitors of lipopolysaccharide-mediated human dendritic cell activation in vitro and of acute inflammation in mice in vivo},
author = {Evelyne Schaeffer and Elena M Sánchez-Fernández and Rita Gonçalves-Pereira and Vincent Flacher and Delphine Lamon and Monique Duval and Jean-Daniel Fauny and José M García Fernández and Christopher G Mueller and Carmen Ortiz Mellet},
doi = {10.1016/j.ejmech.2019.02.078},
issn = {1768-3254},
year = {2019},
date = {2019-05-01},
journal = {European Journal of Medicinal Chemistry},
volume = {169},
pages = {111--120},
abstract = {Glycolipid mimetics consisting of a bicyclic polyhydroxypiperidine-cyclic carbamate core and a pseudoanomeric hydrophobic tail, termed sp2-iminosugar glycolipids (sp2-IGLs), target microglia during neuroinflammatory processes. Here we have synthesized and investigated new variants of sp2-IGLs for their ability to suppress the activation of human monocyte-derived dendritic cells (DCs) by lipopolysaccharide (LPS) signaling through Toll-like receptor 4. We report that the best lead was (1R)-1-dodecylsulfonyl-5N,6O-oxomethylidenenojirimycin (DSO2-ONJ), able to inhibit LPS-induced TNFα production and maturation of DCs. Immunovisualization experiments, using a mannoside glycolipid conjugate (MGC) that also suppress LPS-mediated DC activation as control, evidenced a distinct mode of action for the sp2-IGLs: unlike MGCs, DSO2-ONJ did not elicit internalization of the LPS co-receptor CD14 or induce its co-localization with the Toll-like receptor 4. In a mouse model of LPS-induced acute inflammation, DSO2-ONJ demonstrated anti-inflammatory activity by inhibiting the production of the pro-inflammatory interleukin-6. The ensemble of the data highlights sp2-IGLs as a promising new class of molecules against inflammation by interfering in Toll-like receptor intracellular signaling.},
keywords = {Activation, Acute Disease, Animals, antagonists & inhibitors, CD14, Cells, chemical synthesis, Chemistry, CO-RECEPTOR, Cultured, Dendritic cell, Dendritic Cells, Dose-Response Relationship, Drug, drug effects, drug therapy, Glycolipid, Glycolipids, Human, Humans, Iminosugar, immunopathology, IN VITRO, In vivo, Inbred C57BL, inflammation, Interleukin-6, lipopolysaccharide, Lipopolysaccharides, LPS, Male, Maturation, metabolism, Mice, MICROGLIA, Molecular Structure, mouse, pathology, Pharmacology, PRODUCTION, Receptor, signaling, Structure-Activity Relationship, Sulfone, Sulfoxide, Tail, target, Team-Mueller},
pubstate = {published},
tppubtype = {article}
}