Planning and Topics
SPIM 2018 - 6th edition
APOPTOSIS versus SENESCENCE
8.45 am – Opening of the Meeting
9.00 – 10.30 am: Invited Speakers
Dr Corine BERTOLOTTOINSERM U1065, Biology and Pathologies of melanocytes, Nice, France
“The role of MITF and its sumoylation in the regulation of melanocyte senescence“ View more
Oncogene-induced senescence (OIS) is a mechanism of tumor suppression that restricts the progression of benign tumors including nevus, and thus may account for the high overall survival of affected patients. Consequently, alterations affecting the senescence pathway have been associated with enhanced tumor susceptibility and progression. Cutaneous malignant melanoma represents one of the most deadly forms of skin cancer. In contrast to the metastatic form, early skin localized malignant melanoma, can usually be cured with surgery alone. Extraordinarily breakthroughs in the treatment of metastatic melanoma have been realized these last years thanks to the basic biomedical science. However, clinical responses are still either transient or limited to restricted patient subsets. Hence, early detection and ongoing surveillance of moles for malignant degeneration are strategies to reduce tumor burden of advance disease and for optimal clinical outcome. In 25% of the cases, melanoma originates from a pre-existing nevus. Consequently, primary melanoma can be viewed as a paradigm of senescence evasion. Importantly, this topic appears central to melanoma development, because in human, several known melanoma susceptibility genes are linked to cellular senescence. The master transcriptional regulator of melanocyte lineage survival, pigmentation and melanoma development MITF has been recently identified as a melanoma predisposition gene. In human, the MITFE318K variant that reduces the SUMOylation of MITF is nevogenic. Using cell cultures and a new mouse model, we discovered how this mutation, in association with other alterations, impairs oncogene-induced senescence and exerts its pro-melanoma effect.View less
Pr Corinne ABBADIEUMR 8161, Lille University, CNRS, Institut Pasteur of Lille, France
“Senescence of skin Keratinocytes and fibroblasts“ View more
In contrast to dermal fibroblasts which undergo a replicative senescence associated to an irreversible very stable cell cycle arrest, the epidermal keratinocytes undergo a transient oxidative stress-induced senescence with two possible outcomes: an autophagic cell death for almost all cells and a neoplastic escape for about 1 cell on 10,000. We have shown that senescence in keratinocytes is triggered by an accumulation of DNA single-strand breaks. Unexpectedly, this accumulation of DNA damage is also responsible for the neoplastic escape. The single strand-breaks remain unrepaired because of a decrease in expression of PARP1, the enzyme that recognizes these breaks and initiate their repair. We propose that the default in the single-strand break repair pathway plays a role in skin aging as well as in non-melanocytic cancer appearance.View less
Pr Johannes GRILLARIUniversity of Natural Resources and Life Sciences Vienna, Austria
“Skin cell senescence: a driver of skin aging and how to drive back“ View more
Cellular senescence has evolved from an in vitro model system to study aging to a multifaceted phenomenon of in vivo importance since senescent cells in vivo have been identified and their removal delays the onset of age-associated diseases in a mouse model system. In order to understand how senescent cells that accumulate within organisms with age negatively impact on organ and tissue function, we have started to characterize secreted miRNAs within extracellular vesicles that are differentially expressed in early passage versus senescent cells and their functional role in the context of cellular and organismal aging. Thereby, we identified circulating miRNAs as bona fide members of the senescence associated secretory phenotype (SASP) that are transferred from senescent cells to their microenvironment or even the systemic environment. These miRNAs, among them miR-23a-5p, are transported via extracellular vesicles also in organotypic human skin equivalents and recipient cells taking them up are altered in their cell fate, including altered wound healing and apoptototic behaviour. In addition, we found a plant extract from Solidago alpestris to alleviate some of the detrimental effects of senescent cells in vitro.
In summary, we present evidence of the importance of specific miRNAs and highlight their potential use as biomarkers of aging and age-associated diseases, or even as therapeutic tools and targets to prevent age-associated diseases.View less
10.30 – 11.00 am – Posters session
11.00 – 12.30 pm – 3 young researchers session
2.00 – 3.30 pm: Invited Speakers
Dr Cédric DELEVOYEInstitut Curie, PSL Research University, CNRS, UMR144 - Paris
"Skin cells communication tunes the mechano-signaling properties of melanocytes during pigmentation" View more
Skin physiology, pigmentation and photo-protection rely on the tight communication and close physical contacts between two epidermal cell types, keratinocytes and melanocytes. Indeed, soluble factors or extracellular vesicles (e.g. exosomes) secreted by keratinocytes activate signaling pathways in melanocytes that stimulate melanin pigment synthesis and storage. And concurrently, the remodeling of melanocytes plasma membrane supports dendricity, cell interactions and melanin transfer to keratinocytes. These dynamic features must be finely orchestrated, yet the underlying molecular details are poorly understood.
We first explore the ultrastructure of the melanocyte-keratinocyte interface in human and synthetic skins using 2D and 3D electron microscopy approaches and reveals the specific accumulation of plasma membrane domains. Further investigating their function in normal human melanocytes show their contribution to signal transduction and mechanosensing. Impairing the formation and function of these domains enhances signaling pathways required for melanocyte pigmentation, while decreasing melanin transfer and cell contacts with keratinocytes. Interestingly, the stimulation of melanocytes with physiological doses of UV-B enhances the formation of such domains, whereas factors secreted by keratinocytes decrease their biogenesis, therefore blocking their function. Consequently, reconstructed pigmented epidermis unable to form plasma membrane microdomains display inhomogeneous pigmentation due to improper melanin transfer.
Overall, our study establishes a novel mechano-signaling platform of the melanocyte that controls cell-cell contacts and signaling, exchange of pigment and thus skin homeostasis.View less
Pr Kenji KABASHIMADepartment of Dermatology, Kyoto University Graduate School of Medicine, Japan
“Interactions between immune cells and non-immune cells in the skin“ View more
The skin is the outermost organ of the body and is continuously exposed to external pathogens. Upon inflammation, various immune cells pass through, reside in, or are recruited to the skin to orchestrate diverse cutaneous immune responses. To achieve this, immune cells interact with each other and even communicate with non-immune cells, including peripheral nerves and the microbiome. Immunologically important anatomical sites, such as skin appendages (e.g., hair follicles and sweat glands) or postcapillary venules, act as special portal sites for immune cells and for establishing tertiary lymphoid structures, including inducible skin-associated lymphoid tissue (iSALT). Here, we overview the key findings and concepts of cutaneous immunity in association with skin anatomy and discuss how cutaneous immune cells drive fine-tuning in the skinView less
Dr Catherine MOALIINSERM US8/CNRS UMS3444/ENS Lyon/UCBL, France
“Proteolytic regulation of collagen deposition in wound healing“ View more
The imbalance between collagen assembly and degradation during skin wound healing is a major factor contributing to scarring or chronic wounds. Fibrillar collagen precursors are synthesized by fibroblasts and processed in the extracellular space by specific metalloproteases (e.g. BMP-1/tolloid-like proteinases or BTPs) to form collagen fibrils. Some of these proteolytic maturations can be efficiently stimulated by extracellular glycoproteins called procollagen C-proteinase enhancers (PCPEs). Both BTPs and PCPEs were previously linked to fibrosis but their role in the context of skin wound healing remains elusive. I will describe their expression pattern in resting and wounded skin, explain the mechanism of action of the C-terminal maturation complex of fibrillar collagens and discuss potential consequences for skin scarring.View less
3.30 – 4.00 pm – Posters session
4.00 – 5.30 pm – 3 Young researchers session
5.30 – 7.00 pm – Meeting with the Iceland painter “ERRO“, one of the pioneers of the “Narrative Figuration“ movement.
8.00 pm – Gala Dinner (ALETTI PALACE)
9.00 – 10.30 am: Invited Speakers
Dr Yuan CHAOShanghai Skin Disease Hospital, China
“Diversity of skin microbiome and its association with skin physical parameters in Shanghai healthy women“ View more
This study was to evaluate cutaneous microbial distribution, and microbial co-occurrence at different body sites and skin environments in Shanghai women (N = 100) during the winter season. Methods: Six microbial distribution (Propionibacterium acnes, Staphylococcus aureus, Staphylococcus epidermidis, Lactobacillus, Pseudomonadaceae, and Malassezia furfur), association with biomarkers (antimicrobial peptides: LL-37, β-defensins [HBD-2, HBD-3]), and claudin-1) and skin biophysical parameters (transepidermal water loss, pH, skin scaliness and roughness, sebum and hydration levels) were also determined. Six skin sites (glabella [GL], hand-back [HB], interdigital web-space [IS], antecubital fossa [AF], volar forearm [VF], back [BA]) were classified as normal, oily or dry based on two-step cluster analysis and exposed or unexposed (uncovered or covered by clothes, respectively) based on seasonal apparel. Results: Pseudomonadaceae and Staphylococcus aureus had the highest and lowest detection rate respectively at all sites. Cluster analysis identified skin sites as ‘normal’ (HB, BA, AF, and VF), ‘dry’ (IS) and ‘oily’ (GL). Bacterial alpha diversity was higher in exposed (HB, IS, and GL) compared with unexposed sites (BA, AF and VF). Co-occurrence of Staphylococcus aureus with any of the other five microorganisms was lower in dry and oily skin versus normal skin. Conclusion: Skin exposure, biophysical/barrier profile and biomarkers were found to be associated with bacterial distribution and co-occurrence in Chinese women.View less
Pr Ralf LUDWIGLübeck University, Germany
“Cutaneous and gut microbiota in cutaneous auto-immune disease: a new example of the gut-skin axis“ View more
Genome-wide association and mapping studies identified genetic variants associated with complex trait – such as skin inflammation, conveying insights into their genetic architecture. In addition, interactions between genotype and environment have been recognized as an important cause of variation of complex traits – for example, the impact of diet on body weight, metabolic syndrome, as well as susceptibility to develop chronic inflammatory skin diseases such as psoriasis. To comprehensively understand the impact of genetic variability and diet on phenotypic variability in general, as well as on skin inflammation, outbred mice were exposed to different diets. Expectedly, genetic association was identified for complex traits. Based on full-genome sequencing, associations were linked to single mutations. Notably, considering diet to determine gene-phenotype association, lead to a considerable shift of genetic association. Next, to determine the functional impact of diet on complex phenotypes, lupus-prone mice were exposed to different diets. In these mice, diet substantially modulated lupus manifestation. Mechanistically, diet-induced changes of intestinal bacterial and fungal communities preceded lupus onset by regulating expression of disease susceptibility genes. Collectively, diet has a substantial impact on complex traits by regulating intestinal microbiome and gene expression.View less
Pr Rolf LOODLund University, Sweden
“Cutibacterium acnes and oxidative stress. A gate keeper for Healthy skin“ View more
The association between microbes and development of diseases is well established. However, the beneficial and protective aspects of the microbiota have not been carefully evaluated. My research aims to identify and characterize novel benevolence factors, bacterial factors providing a symbiotic and health promoting relation between the host and the microflora. These factors are prime candidates for novel therapies.
This presentation will discuss the beneficial aspects of Cutibacterium acnes, mediated by the secreted antioxidant RoxP. Presence of RoxP can protect human cells from lethal oxidative damage. Our results suggest that RoxP is beneficial for the host as well as for the bacterium, thus representing a bona fide mutualistic factor for the host-commensal interaction as well for skin redox homeostasis.View less
10.30 – 11.00 am – Posters session
11.00 – 12.30 pm – 3 young researchers session
SKIN & NEURO-SENSITIVITY
2.00 – 3.30 pm: Invited Speakers
Dr Charles EL RAWADIL’Oreal Research & Innovation, Aulnay, France
“Tactile Sensitivity & Skin Aging“ View more
There is a decrease in tactile acuity with ageing: palpation, appreciation of textures, discrimination of objects’ forms, feeling heat and pain…. These changes lead to functional and sensorial disorders, disconnecting the elderly from their skin and emotions induced by touch. The aim of this work was to characterize the decrease in tactile acuity with aging, determine its causes in order to restore the emotions linked to touch, awaken the skin and improve the quality of life of elderly.
We will describe a new evaluation methodology assessing the dynamic touch, well adapted to the usual gesture for example during the application of a cosmetic cream on skin. In a first study including healthy women of different age ranges, we identified two clusters of elderly with (low performing) and without (high performing) decrease in tactile acuity. While the mechanical properties of skin change drastically with age, the comparison of skin properties of these two clusters, indicate that they are not the primary reason for the decrease in tactile sensitivity.
In a second study, we included groups of healthy women selected based on identification as low performing or high performing tactile acuity. We were able to identify the underlying mechanisms behind this declined acuity with aging, and relate it to a decreased somatosensory function.
In conclusion, in addition to short term skin mechanical routes of tactile restoration, these new findings open new field to explore skin aging through peripheral nerves signaling (opening longer term restoration efficacy).
Pr Stevens REHENFederal University of Rio de Janeiro, Brazil
“Reprogrammed stem cells for the development of biomimetic models of human issues“ View more
Reprogrammed stem cells can be derived from the skin or urine samples of humans. Biomimetic tissues, such as brain neurospheres and organoids, can be generated from those reprogrammed stem cells. Recently, we developed biomimetic neural tissues to better understand how Zika virus damages the fetal brain and to test drugs as potential treatments against the infection. We also used them to describe proteomic changes caused by the administration of psychedelics to the brain tissue. Human sensory neurons can be obtained from reprogrammed cells and biomimetic tissues. These cells may become a tool to model human sensory response in vitro. I will present published and unpublished data with biomimetic tissues generated in our laboratory to study brain development and mental diseases.View less
Pr Gil YOSIPOVITCHUniversity of Miami Miller School of Medicine, United States
“Itchy skin and the pleasure of scratching More than the Surface“ View more
Itch—a sensation resulting in an urge to scratch—is normally a benign unpleasant physiologic response. However, when itch becomes severe or chronic (>6 weeks) it has a significant impact on quality of life. The cause of itch involves interactions between keratinocytes, nerve fibers and the immune system. The most well supported distinction between types of itch is that of histaminergic and non-histaminergic itch. Histaminergic itch is mainly related to acute types of itch such as insect bites and non-histaminergic sensory nerves are responsible for the pathophysiology of the majority of chronic types of itch. This presentation provides an overview of specific contributions of keratinocytes, immune pathways, and the nervous system in itch, with emphasis on how they influence each other and how this cross-talk drives the pathophysiology of chronic itch. Therapies with potential to manage -associated itch by targeting the relevant neural skin and immune targets will be discussed.View less
4.00 – 5.30 pm – Awards Ceremony
5.30 pm – Closing of the Meeting