Therapeutic potential of targeting IL ‐1 family cytokines in chronic inflammatory skin diseases

Umbilical cord blood (UCB) has long been seen as a rich source of naive cells with strong regenerative potential, likely mediated by small extracellular vesicles (sEV). More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell sEV (herein referred as Exo-101), and explore their therapeutic potential for inflammatory skin diseases. Exo-101 was shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with Exo-101 resulted in an reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, Exo-101 reduced the expression of inflammatory and psoriatic markers IL-6, IL-8, CXCL10, COX-2, S100A7 and DEFB4. In vivo, Exo-101 significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of Exo-101, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

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The therapeutic potential and molecular mechanism of flavonoid HCF-A on inflammatory skin diseases

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2017.02.051 ◽

2017 ◽

Vol 86 (2) ◽

pp. e18

Author(s):

Hsin-Ju Li ◽

Chi-Feng Hung

Keyword(s):

Molecular Mechanism ◽

Skin Diseases ◽

Therapeutic Potential ◽

Inflammatory Skin Diseases ◽

Inflammatory Skin

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Immunomodulatory Properties of Umbilical Cord Blood-Derived Small Extracellular Vesicles and Their Therapeutic Potential for Inflammatory Skin Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms22189797 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9797

Author(s):

Sílvia C. Rodrigues ◽

Renato M. S. Cardoso ◽

Patricia C. Freire ◽

Cláudia F. Gomes ◽

Filipe V. Duarte ◽

...

Keyword(s):

Cord Blood ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Umbilical Cord Blood ◽

Skin Diseases ◽

Therapeutic Potential ◽

Psoriatic Skin ◽

Inflammatory Skin Diseases ◽

Inflammatory Skin ◽

Anti Inflammatory

Umbilical cord blood (UCB) has long been seen as a rich source of naïve cells with strong regenerative potential, likely mediated by paracrine signals. More recently, small extracellular vesicles (sEV), such as exosomes, have been shown to play essential roles in cell-to-cell communication, via the transport of numerous molecules, including small RNAs. Often explored for their potential as biomarkers, sEV are now known to have regenerative and immunomodulating characteristics, particularly if isolated from stem cell-rich tissues. In this study, we aim to characterize the immunomodulating properties of umbilical cord blood mononuclear cell-derived sEV (UCB-MNC-sEV) and explore their therapeutic potential for inflammatory skin diseases. UCB-MNC-sEV were shown to shift macrophages toward an anti-inflammatory phenotype, which in turn exert paracrine effects on fibroblasts, despite previous inflammatory stimuli. Additionally, the incubation of PBMC with UCB-MNC-sEV resulted in a reduction of total CD4+ and CD8+ T-cell proliferation and cytokine release, while specifically supporting the development of regulatory T-cells (Treg), by influencing FOXP3 expression. In a 3D model of psoriatic skin, UCB-MNC-sEV reduced the expression of inflammatory and psoriatic markers IL6, IL8, CXCL10, COX2, S100A7, and DEFB4. In vivo, UCB-MNC-sEV significantly prevented or reversed acanthosis in imiquimod-induced psoriasis, and tendentially increased the number of Treg in skin, without having an overall impact on disease burden. This work provides evidence for the anti-inflammatory and tolerogenic effect of UCB-MNC-sEV, which may be harnessed for the treatment of Th17-driven inflammatory skin diseases, such as psoriasis.

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Positive Influence of Probiotics on the Gut-Skin Axis

Kompass Nutrition & Dietetics ◽

10.1159/000513185 ◽

2020 ◽

Vol 1 (1) ◽

pp. 25-26

Author(s):

Michael Sticherling

Keyword(s):

Skin Diseases ◽

Therapeutic Potential ◽

Acne Vulgaris ◽

Skin Inflammation ◽

Skin Condition ◽

Positive Influence ◽

Inflammatory Skin Diseases ◽

Synthetic Drugs ◽

Inflammatory Skin ◽

Diseased State

The existence of a gut-skin axis is supported by increasing evidence, but its translational potential is not widely recognized. Studies linked inflammatory skin diseases to an imbalanced gut microbiome; hence, the modulation of the gut microbiota to improve skin condition seems to be a feasible approach. Today, there is a growing interest in natural products as alternatives to synthetic drugs. In this respect, oral probiotics could be a simple, safe and cheap modality in the therapeutic management of skin inflammation. Unfortunately, very few studies have looked into how probiotic supplementation influences inflammatory skin disorders. The results, though promising, are difficult to implement in clinical practice due to the heterogeneity of the applied supplemental regimen in the different studies. In this Viewpoint, we aim to encourage the conduction of more research in that direction to explore unambiguously the therapeutic potential of oral probiotics in dermatology. We focus on the most common inflammatory skin diseases (atopic dermatitis, psoriasis, rosacea, acne vulgaris) with an associated gut dysbiosis, but we also discuss some less common, but very serious skin pathologies (eg erythema nodosum, pyoderma gangrenosum, hidradenitis suppurativa) that are possibly linked to a disturbed gut flora composition. We dissect the possible mechanisms along the gut-skin axis and highlight novel points where probiotics could interfere in this communication in the diseased state.

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Stem Cells-Derived Extracellular Vesicles: Potential Therapeutics for Wound Healing in Chronic Inflammatory Skin Diseases

International Journal of Molecular Sciences ◽

10.3390/ijms22063130 ◽

2021 ◽

Vol 22 (6) ◽

pp. 3130

Author(s):

Enzo Manchon ◽

Nell Hirt ◽

Jean-David Bouaziz ◽

Nabila Jabrane-Ferrat ◽

Reem Al-Daccak

Keyword(s):

Stem Cells ◽

Extracellular Vesicles ◽

Skin Diseases ◽

Therapeutic Potential ◽

Cell Types ◽

Parental Cell ◽

Inflammatory Skin Diseases ◽

Beneficial Effects ◽

Cell Source ◽

Inflammatory Skin

Endosome-derived small extracellular vesicles (EVs), often referred to as exosomes, are produced by almost all, if not all, cell types, and are critical for intercellular communication. They are composed of a lipid bilayer associated with membrane proteins and contain a payload of lipids, proteins and regulatory RNAs that depends on the parental cell physiological condition. By transferring their “cargo”, exosomes can modulate the phenotype of neighboring and distant cells. Stem cells (SC) were widely studied for therapeutic applications regarding their regenerative/reparative potential as well as their immunomodulatory properties. Whether from autologous or allogeneic source, SC beneficial effects in terms of repair and regeneration are largely attributed to their paracrine signaling notably through secreted EVs. Subsequently, SC-derived EVs have been investigated for the treatment of various diseases, including inflammatory skin disorders, and are today fast-track cell-free tools for regenerative/reparative strategies. Yet, their clinical application is still facing considerable challenges, including production and isolation procedures, and optimal cell source. Within the emerging concept of “allogeneic-driven benefit” for SC-based therapies, the use of EVs from allogeneic sources becomes the pragmatic choice although a universal allogeneic cell source is still needed. As a unique temporary organ that ensures the mutual coexistence of two allogeneic organisms, mother and fetus, the human placenta offers a persuasive allogeneic stem cell source for development of therapeutic EVs. Advancing cell-free therapeutics nurtures great hope and provides new perspectives for the development of safe and effective treatment in regenerative/reparative medicine and beyond. We will outline the current state of the art in regard of EVs, summarize their therapeutic potential in the context of skin inflammatory disorders, and discuss their translational advantages and hurdles.

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