Yves Poumay | Université de Namur (University of Namur) (original) (raw)

Papers by Yves Poumay

Research paper thumbnail of 887 Trichophyton rubrum infection on reconstructed human epidermis induces simultaneous epidermal barrier disruption and keratinocytes activation

Journal of Investigative Dermatology, May 1, 2018

Research paper thumbnail of TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation

PLOS ONE, Jan 19, 2016

TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously ... more TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.

Research paper thumbnail of Modeling dermatophytosis in reconstructed human epidermis: A new tool to study infection mechanisms and to test antifungal agents

Medical Mycology, Oct 19, 2016

Dermatophytosis is a superficial fungal infection of keratinized structures that exhibits an incr... more Dermatophytosis is a superficial fungal infection of keratinized structures that exhibits an increasing prevalence in humans and is thus requesting novel prophylactic strategies and therapies. However, precise mechanisms used by dermatophytes to adhere at the surface of the human epidermis and invade its stratum corneum are still incompletely identified, as well as the responses provided by the underlying living keratinocytes during the infection. We hereby report development of an in vitro model of human dermatophytosis through infection of reconstructed human epidermis (RHE) by arthroconidia of the anthropophilic Trichophyton rubrum species or of the zoophilic Microsporum canis and Arthroderma benhamiae species. By modulating density of arthroconidia in the inoculum and duration of exposure to such pathogens, fungal infection limited to the stratum corneum was obtained, mimicking severe but typical in vivo situation. Fungal elements in infected RHE were monitored over time by histochemical analysis using periodic-acid Schiff-staining or quantified by qPCR-detection of fungal genes inside RHE lysates. This model brings improvements to available ones, dedicated to better understand how dermatophytes and epidermis interact, as well as to evaluate preventive and therapeutic agents. Indeed, miconazole topically added to RHE was demonstrated to inhibit fungal infection in this model.

Research paper thumbnail of 193 Epidermal invasion by Malassezia spp. yeasts in 3D-reconstructed tissue

Journal of Investigative Dermatology, May 1, 2021

Research paper thumbnail of La protéine TSG-6 induite par l’inflammation contribue au maintien de l’hyaluronan dans l’épiderme humain

Annales De Dermatologie Et De Venereologie, Nov 1, 2020

TSG-6 est une proteine anti-inflammatoire impliquee dans le remodelage de la matrice extracellula... more TSG-6 est une proteine anti-inflammatoire impliquee dans le remodelage de la matrice extracellulaire. Cette proteine lie l’hyaluronan (HA), le principal glycosaminoglycan present dans les espaces intercellulaires des keratinocytes epidermiques. Dans les epidermes humains reconstruits (RHE) en conditions normales, l’ARNm de TSG-6 est exprime a un niveau basal et une faible quantite de cette proteine est detectee dans le milieu de culture. Des conditions inflammatoires, telles que l’exposition a des cytokines de reponse immune Th2 (dermatite atopique) ou l’infection des RHE par des dermatophytes, montrent une augmentation de la production d’HA simultanee a une induction de l’expression de TSG-6, ainsi qu’une secretion accrue de la proteine dans le milieu de culture. Pour elucider la fonction de TSG-6 dans l’epiderme, le genome de keratinocytes immortalises (N/TERT) a ete edite par la methode CRISPR/Cas 9 pour creer des cellules TSG-6-/- et les utiliser pour produire des RHE. Les RHE composes des keratinocytes TSG-6-/- montrent une morphologie semblable aux RHE controles. Une quantite accrue d’HA est detectee dans le milieu sous-jacent des tissus KO, simultanement a une reduction du contenu en HA intra-tissulaire. Le maintien d’une quantite accrue d’HA dans l’epiderme semble etre une piste interessante pour specifier le role de TSG-6 dans l’epiderme.

Research paper thumbnail of 229 Elaboration of reconstructed sheep epidermis

Journal of Investigative Dermatology, Sep 1, 2019

Rosacea is a common, chronic inflammatory skin disease usually developing in adults mainly affect... more Rosacea is a common, chronic inflammatory skin disease usually developing in adults mainly affecting sebaceous gland rich (SGR) skin areas, such as cheeks, nose, chin, and forehead. Although clinical data (skin dryness) and previous functional studies (elevated pH and TEWL, decreased hydration) of affected skin indicated barrier alterations, the detailed molecular analysis of barrier damage is completely missing. We aimed to investigate the permeability barrier alterations of rosacea skin. RNASeq has been performed on 8 SGR and 8 rosacea skin samples to reveal gene expressional differences. Functional pathway enrichment analyses were performed by ClueGo application of Cytoscape software. Validation of expression levels was assessed by RT-PCR and immunohistochemistry. 5136 gene showed significantly different expression; 3133 genes showed higher, whereas 2003 genes exhibited lower expressions in rosacea samples (fold change ! 1,5). Pathway analysis revealed multiple genes exhibiting roles in the formation of the skin barrier and cell junctions. Thus, we focused on validating the expression of these genes. In rosacea, proliferation markers (KRT6, 16, 17, 79), showed significantly higher expression while differentiation markers (FLG, LCE1, LOR, KRT1, 10) and cell junction molecules (CLDN1, 16, 23, CDH1, CDSN, DSC1, DSG1, PKP1, OCLN) were significantly downregulated compared to SGR. The expression of antimicrobial peptides (S100A7,8,9, hBD2, LCN2, LL37) was also significantly higher in rosacea. Besides the wellknown dysregulation of immunological, vascular and neurological functions, we could prove at the molecular level that a prominent barrier alteration also exists in rosacea, which highlights the importance of barrier repair therapies and their further development in the future.

Research paper thumbnail of 125 Characterization of TSG-6 protein in healthy and inflammatory models of reconstructed human epidermis

Journal of Investigative Dermatology, Oct 1, 2017

A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and ski... more A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and skin infections, failure to thrive, constant vomiting and brain abnormalities. He had persistent thrombocytosis, hypoalbunemia and hypernatremia. IgE levels rose at age 0.6 years (985 kU/l) without eosinophilia. Cow milk allergy was diagnosed at 0.7 years. IVIG treatment from 0.6 years reduced infections and acitretin from age 0.7 years reduced scaling. Skin biopsy showed a psoriformic reaction with normal LEKTI but absent filaggrin staining. Vast immunological and metabolic analyses and ichtyosis and immunodeficiency gene panels were normal. Whole exome sequencing showed a heterozygous Desmoplakin missense variant c.1756C>T, p.(His586Tyr). A heterozygous mutation in the neighboring nucleotide c.1757C>T, p.(His586Pro) with a similar phenotype was reported in one patient. The phenotype is typical for severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome to date reported in five other patients with homozygous Desmoglein 1 mutations. Desmoplakins and desmogleins are key molecules in desmosomes, which are adhesive intercellular junctions crucial in tissues prone to mechanical stress (e.g. skin, heart, gastrointestinal mucosa). Desmosomal proteins play a role in cell signalling and skin barrier function. Reported SAM patients developed dermatitis and erythroderma neonatally with failure to thrive (86%, 6/7), recurrent infections (86%, 6/7), elevated IgE (86%, 6/7), hypotrichosis (71%, 5/7), food allergy (71%, 5/7), developmental delay (71%, 5/7), variable gastrointestinal features (57%, 4/7), hypoalbuminemia (57%, 4/7) and hyper-/hyponatremia (43%, 3/7). The SAM syndrome is clinically similar to Netherton syndrome caused by SPINK5 mutations leading to a severe epidermal barrier defect. Desmoplakin mutations should be included in the differential diagnosis of erythrodermic, allergy and infection prone infants with skin barrier defects.

Research paper thumbnail of 394 Analysis of keratinocyte response to Trichophyton rubrum dermatophyte infection in a model of reconstructed human epidermis

Journal of Investigative Dermatology, Oct 1, 2017

Research paper thumbnail of Hyaluronan Metabolism in Human Keratinocytes and Atopic Dermatitis Skin Is Driven by a Balance of Hyaluronan Synthases 1 and 3

Journal of Investigative Dermatology, Aug 1, 2014

Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the extracellular matrix by thre... more Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the extracellular matrix by three hyaluronan synthases (HAS1, HAS2, and HAS3). HA is abundantly synthesized by keratinocytes but its epidermal functions remain unclear. We used culture models to grow human keratinocytes as autocrine monolayers or as reconstructed human epidermis (RHE) to assess HA synthesis and HAS expression levels during the course of keratinocyte differentiation. In both the models, epidermal differentiation downregulates HAS3 mRNA expression while increasing HAS1 without significant changes in hyaluronidase expression. HA production correlates with HAS1 mRNA expression level during normal differentiation. To investigate the regulation of HAS gene expression during inflammatory conditions linked to perturbed differentiation, lesional and non-lesional skin biopsies of atopic dermatitis (AD) patients were analyzed. HAS3 mRNA expression level increases in AD lesions compared with healthy and non-lesional skin. Simultaneously, HAS1 expression decreases. Heparin-binding EGFlike growth factor (HB-EGF) is upregulated in AD epidermis. An AD-like HAS expression pattern is observed in RHE incubated with HB-EGF. These results indicate that HAS1 is the main enzyme responsible for HA production by normal keratinocytes and thus, must be considered as an actor of normal keratinocyte differentiation. In contrast, HAS3 can be induced by HB-EGF and seems mainly involved in AD epidermis.

Research paper thumbnail of Keratinocytes activated by <scp>IL</scp> ‐4/ <scp>IL</scp> ‐13 express <scp>IL‐2Rγ</scp> with consequences on epidermal barrier function

Experimental Dermatology, Jan 26, 2023

Research paper thumbnail of Développement et analyse d’un modèle in vitro d’infection épidermique par dermatophytes anthropophiles

Annales De Dermatologie Et De Venereologie, Jun 1, 2015

Déclaration d'intérêts Les auteurs n'ont pas transmis de déclaration de conflits d'intérêts.

Research paper thumbnail of 294 TSG-6 invalidation in immortalized keratinocytes using CRISPR/Cas9 method

Journal of Investigative Dermatology, Sep 1, 2019

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin disorder clinically characteri... more Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin disorder clinically characterized by keratotic follicular papules, well-demarcated scaly erythematous plaques interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. The autosomal dominant subtype, which is classified as PRP type V (PRPV), is associated with gain-of-function mutations in CARD14. Although around 30 cases with PRPV have been reported in the literature, diagnosis and treatment remain difficult. In this study, we analysed a 60-year-old Japanese male with erythroderma, palmoplantar keratoderma, ectropion and joint contractures of the fingers, all of which had appeared since birth. Notably, he has experienced multiple skin tumours including malignant melanoma and squamous cell carcinoma. Although the patient was initially diagnosed with congenital ichthyosiform erythroderma (CIE), mutation analysis unexpectedly revealed a heterozygous mutation c.356T>C (p.Met119Thr) in CARD14, whereas no pathogenic mutations were detected in any of the 12 genes responsible for CIE. This de novo mutation was absent from available databases. Overexpression of this mutant CARD14 formed aggregations in the cytoplasm, which exhibited a completely different distribution from that of the wild type. Furthermore, the NF-kB luciferase reporter assay revealed that mutant CARD14 showed a 2-fold increase in NF-kB activity compared with the wild type, suggesting the pathogenicity of the mutation. These findings led to the final diagnosis of PRPV. We have treated the present case with ustekinumab, which we have found partially effective. This study further expands our understanding of clinical and genetic features of PRPV. The multiple occurrences of skin tumours with this patient may suggest potential tumorigenesis associated with the disease.

Research paper thumbnail of Analyse de la réponse des kératinocytes face à l’infection par le dermatophyte anthropophile Trichophyton rubrum sur un modèle d’épiderme humain reconstruit

Journal De Mycologie Medicale, Sep 1, 2017

Research paper thumbnail of Analyse de la réponse des kératinocytes face à l’infection par les dermatophytes sur un modèle d’épiderme humain reconstruit

Annales De Dermatologie Et De Venereologie, Dec 1, 2016

Research paper thumbnail of 326 Modeling dermatophytosis in reconstructed human epidermis

Journal of Investigative Dermatology, Sep 1, 2016

Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations... more Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations such as Kit W-sh/W-sh. However, these mice reportedly had other hematopoietic abnormalities. To use bona fide solely MC-deficient mice, Cpa3 Cre/+ mice were established using Cre under the control of a promoter of MC-specific Carboxypeptidase A3 (Cpa3) gene and are now used to study MC functions in vivo. We confirmed that peritoneal MCs in both mice were undetectable by flow cytometry and were detectable upon reconstitution of MCs by injecting bone marrow-derived MC (BMMC) from wild type (WT) mice. While analyzing peritoneal MCs in a CD45 + cell population, we discovered that F4/80 hi CD11b hi peritoneal macrophages (mFs) were reduced in both mice compared to WT mice, and were restored to the level of WT mice by the MC reconstitution. We also discovered that c-Kit + CD11b + cells were undetectable in both mice and significantly increased upon the MC reconstitution. We further found that c-Kit+CD11b+ cells expressed CD34, Sca-1, and CD135, indicating the expression of multipotent progenitor (MPP) phenotypes. We termed these cells "MPP-like cells". Upon the MC reconstitution in Cpa3 Cre/+ (CD45.2) mice by CD45.1 BMMC, we identified MPP-like cells were recipient-derived, while upon the MC reconstitution in Kit W-sh/W-sh (CD45.1) mice by CD45.2 BMMC, they were totally donor-derived. These results indicated that MCs are required for the development of MPP-like cells in Cpa3 Cre/+ mice and MCs per se in Kit W-sh/W-sh mice transform into MPP-like cells. We next tested whether the similar phenomenon was observed in the skin. To do so, we reconstituted MCs in both mice by the i.d. injection of WT-derived BMMC. In both, MCs in the skin were restored to the WT level, whereas CD206 + dermal mFs were significantly increased compared to non-reconstituted mice. Taken together, these results suggest that MCs play a role in controlling a population of MPP-like cells as a mF progenitor cell-type to regulate mF homeostasis in terms of its number and phenotype in a tissue-dependent manner. 323 IL-36y stimulation induces proinflammatory effects on human endothelial cells

Research paper thumbnail of Développement d’un modèle de dermatophytose sur épiderme humain reconstruit

Journal De Mycologie Medicale, Jun 1, 2016

Research paper thumbnail of Le métabolisme de l’hyaluronan dans les kératinocytes humains et lors de la dermatite atopique est caractérisée par un équilibre d’expression entre HAS1 et HAS3

Annales De Dermatologie Et De Venereologie, Jun 1, 2014

Research paper thumbnail of Modelling atopic dermatitis during the morphogenetic process involved in reconstruction of a human epidermis

Current Research in Translational Medicine, Oct 1, 2016

Research paper thumbnail of 110 Deletion of TNFAIP6 gene in human keratinocytes by CRISPR/Cas9 edition demonstrates a role for TSG-6 to retain hyaluronan inside epidermis

Journal of Investigative Dermatology

Research paper thumbnail of Maladies et remèdes en tout genre

Presses universitaires de Namur eBooks, 2017

Philippe Gherincx (1549-1604) Description de la nature & facultez des fontaines acides de Spa... more Philippe Gherincx (1549-1604) Description de la nature & facultez des fontaines acides de Spa A Liege : chez Nicolas vander Hulst, [1599] Rés. Varia41 (1599) Voici un ouvrage publié à Liège en toute fin de xvie siècle. Il traite d’un sujet qui semble d’abord plutôt régional, mais qui se retrouve lié à la médecine et à son histoire via le thermalisme et la recherche d’une compréhension des propriétés médicinales (« vertus et miraculeux effets » dit l’auteur) de certaines fontaines acides de S..

Research paper thumbnail of 887 Trichophyton rubrum infection on reconstructed human epidermis induces simultaneous epidermal barrier disruption and keratinocytes activation

Journal of Investigative Dermatology, May 1, 2018

Research paper thumbnail of TMEM45A Is Dispensable for Epidermal Morphogenesis, Keratinization and Barrier Formation

PLOS ONE, Jan 19, 2016

TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously ... more TMEM45A gene encodes an initially uncharacterized predicted transmembrane protein. We previously showed that this gene is highly expressed in keratinocytes where its expression correlates with keratinization, suggesting a role in normal epidermal physiology. To test this hypothesis, we generated TMEM45A knockout mice and found that these mice develop without any evident phenotype. The morphology of the epidermis assessed by histology and by labelling differentiation markers in immunofluorescence was not altered. Toluidine blue permeability assay showed that the epidermal barrier develops normally during embryonic development. We also showed that depletion of TMEM45A in human keratinocytes does not alter their potential to form in vitro 3D-reconstructed epidermis. Indeed, epidermis with normal morphogenesis were generated from TMEM45A-silenced keratinocytes. Their expression of differentiation markers quantified by RT-qPCR and evidenced by immunofluorescence labelling as well as their barrier function estimated by Lucifer yellow permeability were similar to the control epidermis. In summary, TMEM45A gene expression is dispensable for epidermal morphogenesis, keratinization and barrier formation. If this protein plays a role in the epidermis, its experimental depletion can possibly be compensated by other proteins in the two experimental models analyzed in this study.

Research paper thumbnail of Modeling dermatophytosis in reconstructed human epidermis: A new tool to study infection mechanisms and to test antifungal agents

Medical Mycology, Oct 19, 2016

Dermatophytosis is a superficial fungal infection of keratinized structures that exhibits an incr... more Dermatophytosis is a superficial fungal infection of keratinized structures that exhibits an increasing prevalence in humans and is thus requesting novel prophylactic strategies and therapies. However, precise mechanisms used by dermatophytes to adhere at the surface of the human epidermis and invade its stratum corneum are still incompletely identified, as well as the responses provided by the underlying living keratinocytes during the infection. We hereby report development of an in vitro model of human dermatophytosis through infection of reconstructed human epidermis (RHE) by arthroconidia of the anthropophilic Trichophyton rubrum species or of the zoophilic Microsporum canis and Arthroderma benhamiae species. By modulating density of arthroconidia in the inoculum and duration of exposure to such pathogens, fungal infection limited to the stratum corneum was obtained, mimicking severe but typical in vivo situation. Fungal elements in infected RHE were monitored over time by histochemical analysis using periodic-acid Schiff-staining or quantified by qPCR-detection of fungal genes inside RHE lysates. This model brings improvements to available ones, dedicated to better understand how dermatophytes and epidermis interact, as well as to evaluate preventive and therapeutic agents. Indeed, miconazole topically added to RHE was demonstrated to inhibit fungal infection in this model.

Research paper thumbnail of 193 Epidermal invasion by Malassezia spp. yeasts in 3D-reconstructed tissue

Journal of Investigative Dermatology, May 1, 2021

Research paper thumbnail of La protéine TSG-6 induite par l’inflammation contribue au maintien de l’hyaluronan dans l’épiderme humain

Annales De Dermatologie Et De Venereologie, Nov 1, 2020

TSG-6 est une proteine anti-inflammatoire impliquee dans le remodelage de la matrice extracellula... more TSG-6 est une proteine anti-inflammatoire impliquee dans le remodelage de la matrice extracellulaire. Cette proteine lie l’hyaluronan (HA), le principal glycosaminoglycan present dans les espaces intercellulaires des keratinocytes epidermiques. Dans les epidermes humains reconstruits (RHE) en conditions normales, l’ARNm de TSG-6 est exprime a un niveau basal et une faible quantite de cette proteine est detectee dans le milieu de culture. Des conditions inflammatoires, telles que l’exposition a des cytokines de reponse immune Th2 (dermatite atopique) ou l’infection des RHE par des dermatophytes, montrent une augmentation de la production d’HA simultanee a une induction de l’expression de TSG-6, ainsi qu’une secretion accrue de la proteine dans le milieu de culture. Pour elucider la fonction de TSG-6 dans l’epiderme, le genome de keratinocytes immortalises (N/TERT) a ete edite par la methode CRISPR/Cas 9 pour creer des cellules TSG-6-/- et les utiliser pour produire des RHE. Les RHE composes des keratinocytes TSG-6-/- montrent une morphologie semblable aux RHE controles. Une quantite accrue d’HA est detectee dans le milieu sous-jacent des tissus KO, simultanement a une reduction du contenu en HA intra-tissulaire. Le maintien d’une quantite accrue d’HA dans l’epiderme semble etre une piste interessante pour specifier le role de TSG-6 dans l’epiderme.

Research paper thumbnail of 229 Elaboration of reconstructed sheep epidermis

Journal of Investigative Dermatology, Sep 1, 2019

Rosacea is a common, chronic inflammatory skin disease usually developing in adults mainly affect... more Rosacea is a common, chronic inflammatory skin disease usually developing in adults mainly affecting sebaceous gland rich (SGR) skin areas, such as cheeks, nose, chin, and forehead. Although clinical data (skin dryness) and previous functional studies (elevated pH and TEWL, decreased hydration) of affected skin indicated barrier alterations, the detailed molecular analysis of barrier damage is completely missing. We aimed to investigate the permeability barrier alterations of rosacea skin. RNASeq has been performed on 8 SGR and 8 rosacea skin samples to reveal gene expressional differences. Functional pathway enrichment analyses were performed by ClueGo application of Cytoscape software. Validation of expression levels was assessed by RT-PCR and immunohistochemistry. 5136 gene showed significantly different expression; 3133 genes showed higher, whereas 2003 genes exhibited lower expressions in rosacea samples (fold change ! 1,5). Pathway analysis revealed multiple genes exhibiting roles in the formation of the skin barrier and cell junctions. Thus, we focused on validating the expression of these genes. In rosacea, proliferation markers (KRT6, 16, 17, 79), showed significantly higher expression while differentiation markers (FLG, LCE1, LOR, KRT1, 10) and cell junction molecules (CLDN1, 16, 23, CDH1, CDSN, DSC1, DSG1, PKP1, OCLN) were significantly downregulated compared to SGR. The expression of antimicrobial peptides (S100A7,8,9, hBD2, LCN2, LL37) was also significantly higher in rosacea. Besides the wellknown dysregulation of immunological, vascular and neurological functions, we could prove at the molecular level that a prominent barrier alteration also exists in rosacea, which highlights the importance of barrier repair therapies and their further development in the future.

Research paper thumbnail of 125 Characterization of TSG-6 protein in healthy and inflammatory models of reconstructed human epidermis

Journal of Investigative Dermatology, Oct 1, 2017

A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and ski... more A neonatal boy presented with ichthyosiform erythroderma, hypotrichosis, recurrent sepsis and skin infections, failure to thrive, constant vomiting and brain abnormalities. He had persistent thrombocytosis, hypoalbunemia and hypernatremia. IgE levels rose at age 0.6 years (985 kU/l) without eosinophilia. Cow milk allergy was diagnosed at 0.7 years. IVIG treatment from 0.6 years reduced infections and acitretin from age 0.7 years reduced scaling. Skin biopsy showed a psoriformic reaction with normal LEKTI but absent filaggrin staining. Vast immunological and metabolic analyses and ichtyosis and immunodeficiency gene panels were normal. Whole exome sequencing showed a heterozygous Desmoplakin missense variant c.1756C>T, p.(His586Tyr). A heterozygous mutation in the neighboring nucleotide c.1757C>T, p.(His586Pro) with a similar phenotype was reported in one patient. The phenotype is typical for severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome to date reported in five other patients with homozygous Desmoglein 1 mutations. Desmoplakins and desmogleins are key molecules in desmosomes, which are adhesive intercellular junctions crucial in tissues prone to mechanical stress (e.g. skin, heart, gastrointestinal mucosa). Desmosomal proteins play a role in cell signalling and skin barrier function. Reported SAM patients developed dermatitis and erythroderma neonatally with failure to thrive (86%, 6/7), recurrent infections (86%, 6/7), elevated IgE (86%, 6/7), hypotrichosis (71%, 5/7), food allergy (71%, 5/7), developmental delay (71%, 5/7), variable gastrointestinal features (57%, 4/7), hypoalbuminemia (57%, 4/7) and hyper-/hyponatremia (43%, 3/7). The SAM syndrome is clinically similar to Netherton syndrome caused by SPINK5 mutations leading to a severe epidermal barrier defect. Desmoplakin mutations should be included in the differential diagnosis of erythrodermic, allergy and infection prone infants with skin barrier defects.

Research paper thumbnail of 394 Analysis of keratinocyte response to Trichophyton rubrum dermatophyte infection in a model of reconstructed human epidermis

Journal of Investigative Dermatology, Oct 1, 2017

Research paper thumbnail of Hyaluronan Metabolism in Human Keratinocytes and Atopic Dermatitis Skin Is Driven by a Balance of Hyaluronan Synthases 1 and 3

Journal of Investigative Dermatology, Aug 1, 2014

Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the extracellular matrix by thre... more Hyaluronan (HA) is a glycosaminoglycan synthesized directly into the extracellular matrix by three hyaluronan synthases (HAS1, HAS2, and HAS3). HA is abundantly synthesized by keratinocytes but its epidermal functions remain unclear. We used culture models to grow human keratinocytes as autocrine monolayers or as reconstructed human epidermis (RHE) to assess HA synthesis and HAS expression levels during the course of keratinocyte differentiation. In both the models, epidermal differentiation downregulates HAS3 mRNA expression while increasing HAS1 without significant changes in hyaluronidase expression. HA production correlates with HAS1 mRNA expression level during normal differentiation. To investigate the regulation of HAS gene expression during inflammatory conditions linked to perturbed differentiation, lesional and non-lesional skin biopsies of atopic dermatitis (AD) patients were analyzed. HAS3 mRNA expression level increases in AD lesions compared with healthy and non-lesional skin. Simultaneously, HAS1 expression decreases. Heparin-binding EGFlike growth factor (HB-EGF) is upregulated in AD epidermis. An AD-like HAS expression pattern is observed in RHE incubated with HB-EGF. These results indicate that HAS1 is the main enzyme responsible for HA production by normal keratinocytes and thus, must be considered as an actor of normal keratinocyte differentiation. In contrast, HAS3 can be induced by HB-EGF and seems mainly involved in AD epidermis.

Research paper thumbnail of Keratinocytes activated by <scp>IL</scp> ‐4/ <scp>IL</scp> ‐13 express <scp>IL‐2Rγ</scp> with consequences on epidermal barrier function

Experimental Dermatology, Jan 26, 2023

Research paper thumbnail of Développement et analyse d’un modèle in vitro d’infection épidermique par dermatophytes anthropophiles

Annales De Dermatologie Et De Venereologie, Jun 1, 2015

Déclaration d'intérêts Les auteurs n'ont pas transmis de déclaration de conflits d'intérêts.

Research paper thumbnail of 294 TSG-6 invalidation in immortalized keratinocytes using CRISPR/Cas9 method

Journal of Investigative Dermatology, Sep 1, 2019

Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin disorder clinically characteri... more Pityriasis rubra pilaris (PRP) is a rare chronic inflammatory skin disorder clinically characterized by keratotic follicular papules, well-demarcated scaly erythematous plaques interspersed with distinct islands of uninvolved skin, and palmoplantar keratoderma. The autosomal dominant subtype, which is classified as PRP type V (PRPV), is associated with gain-of-function mutations in CARD14. Although around 30 cases with PRPV have been reported in the literature, diagnosis and treatment remain difficult. In this study, we analysed a 60-year-old Japanese male with erythroderma, palmoplantar keratoderma, ectropion and joint contractures of the fingers, all of which had appeared since birth. Notably, he has experienced multiple skin tumours including malignant melanoma and squamous cell carcinoma. Although the patient was initially diagnosed with congenital ichthyosiform erythroderma (CIE), mutation analysis unexpectedly revealed a heterozygous mutation c.356T>C (p.Met119Thr) in CARD14, whereas no pathogenic mutations were detected in any of the 12 genes responsible for CIE. This de novo mutation was absent from available databases. Overexpression of this mutant CARD14 formed aggregations in the cytoplasm, which exhibited a completely different distribution from that of the wild type. Furthermore, the NF-kB luciferase reporter assay revealed that mutant CARD14 showed a 2-fold increase in NF-kB activity compared with the wild type, suggesting the pathogenicity of the mutation. These findings led to the final diagnosis of PRPV. We have treated the present case with ustekinumab, which we have found partially effective. This study further expands our understanding of clinical and genetic features of PRPV. The multiple occurrences of skin tumours with this patient may suggest potential tumorigenesis associated with the disease.

Research paper thumbnail of Analyse de la réponse des kératinocytes face à l’infection par le dermatophyte anthropophile Trichophyton rubrum sur un modèle d’épiderme humain reconstruit

Journal De Mycologie Medicale, Sep 1, 2017

Research paper thumbnail of Analyse de la réponse des kératinocytes face à l’infection par les dermatophytes sur un modèle d’épiderme humain reconstruit

Annales De Dermatologie Et De Venereologie, Dec 1, 2016

Research paper thumbnail of 326 Modeling dermatophytosis in reconstructed human epidermis

Journal of Investigative Dermatology, Sep 1, 2016

Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations... more Mast cell (MC) functions in vivo have been analyzed by using MC-deficient mice with Kit mutations such as Kit W-sh/W-sh. However, these mice reportedly had other hematopoietic abnormalities. To use bona fide solely MC-deficient mice, Cpa3 Cre/+ mice were established using Cre under the control of a promoter of MC-specific Carboxypeptidase A3 (Cpa3) gene and are now used to study MC functions in vivo. We confirmed that peritoneal MCs in both mice were undetectable by flow cytometry and were detectable upon reconstitution of MCs by injecting bone marrow-derived MC (BMMC) from wild type (WT) mice. While analyzing peritoneal MCs in a CD45 + cell population, we discovered that F4/80 hi CD11b hi peritoneal macrophages (mFs) were reduced in both mice compared to WT mice, and were restored to the level of WT mice by the MC reconstitution. We also discovered that c-Kit + CD11b + cells were undetectable in both mice and significantly increased upon the MC reconstitution. We further found that c-Kit+CD11b+ cells expressed CD34, Sca-1, and CD135, indicating the expression of multipotent progenitor (MPP) phenotypes. We termed these cells "MPP-like cells". Upon the MC reconstitution in Cpa3 Cre/+ (CD45.2) mice by CD45.1 BMMC, we identified MPP-like cells were recipient-derived, while upon the MC reconstitution in Kit W-sh/W-sh (CD45.1) mice by CD45.2 BMMC, they were totally donor-derived. These results indicated that MCs are required for the development of MPP-like cells in Cpa3 Cre/+ mice and MCs per se in Kit W-sh/W-sh mice transform into MPP-like cells. We next tested whether the similar phenomenon was observed in the skin. To do so, we reconstituted MCs in both mice by the i.d. injection of WT-derived BMMC. In both, MCs in the skin were restored to the WT level, whereas CD206 + dermal mFs were significantly increased compared to non-reconstituted mice. Taken together, these results suggest that MCs play a role in controlling a population of MPP-like cells as a mF progenitor cell-type to regulate mF homeostasis in terms of its number and phenotype in a tissue-dependent manner. 323 IL-36y stimulation induces proinflammatory effects on human endothelial cells

Research paper thumbnail of Développement d’un modèle de dermatophytose sur épiderme humain reconstruit

Journal De Mycologie Medicale, Jun 1, 2016

Research paper thumbnail of Le métabolisme de l’hyaluronan dans les kératinocytes humains et lors de la dermatite atopique est caractérisée par un équilibre d’expression entre HAS1 et HAS3

Annales De Dermatologie Et De Venereologie, Jun 1, 2014

Research paper thumbnail of Modelling atopic dermatitis during the morphogenetic process involved in reconstruction of a human epidermis

Current Research in Translational Medicine, Oct 1, 2016

Research paper thumbnail of 110 Deletion of TNFAIP6 gene in human keratinocytes by CRISPR/Cas9 edition demonstrates a role for TSG-6 to retain hyaluronan inside epidermis

Journal of Investigative Dermatology

Research paper thumbnail of Maladies et remèdes en tout genre

Presses universitaires de Namur eBooks, 2017

Philippe Gherincx (1549-1604) Description de la nature & facultez des fontaines acides de Spa... more Philippe Gherincx (1549-1604) Description de la nature & facultez des fontaines acides de Spa A Liege : chez Nicolas vander Hulst, [1599] Rés. Varia41 (1599) Voici un ouvrage publié à Liège en toute fin de xvie siècle. Il traite d’un sujet qui semble d’abord plutôt régional, mais qui se retrouve lié à la médecine et à son histoire via le thermalisme et la recherche d’une compréhension des propriétés médicinales (« vertus et miraculeux effets » dit l’auteur) de certaines fontaines acides de S..