In-vivo regulation of CD23/FCϵRII on inflammatory dendritic epidermal cells (IDEC) and langerhans cells (LC) in inflammatory skin diseases

Atopic dermatitis (AD) is a chronic and persistent inflammatory skin disease characterized by eczematous lesions and itching, and it has become a serious health problem. However, the common clinical treatments provide limited relief and are accompanied by adverse effects. Therefore, there is a need to develop novel and effective therapies to treat AD. Neferine is a small molecule compound isolated from the green embryo of the mature seeds of lotus (Nelumbo nucifera). It has a bisbenzylisoquinoline alkaloid structure. Relevant studies have shown that neferine has many pharmacological and biological activities, including anti-inflammatory, anti-thrombotic, and anti-diabetic activities. However, there are very few studies on neferine in the skin, especially the related effects on inflammatory skin diseases. In this study, we proved that it has the potential to be used in the treatment of atopic dermatitis. Through in vitro studies, we found that neferine inhibited the expression of cytokines and chemokines in TNF-α/IFN-γ-stimulated human keratinocyte (HaCaT) cells, and it reduced the phosphorylation of MAPK and the NF-κB signaling pathway. Through in vivo experiments, we used 2,4-dinitrochlorobenzene (DNCB) to induce atopic dermatitis-like skin inflammation in a mouse model. Our results show that neferine significantly decreased the skin barrier damage, scratching responses, and epidermal hyperplasia induced by DNCB. It significantly decreased transepidermal water loss (TEWL), erythema, blood flow, and ear thickness and increased surface skin hydration. Moreover, it also inhibited the expression of cytokines and the activation of signaling pathways. These results indicate that neferine has good potential as an alternative medicine for the treatment of atopic dermatitis or other skin-related inflammatory diseases.

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The role of lactobacilli in inhibiting skin pathogens

Biochemical Society Transactions ◽

10.1042/bst20200329 ◽

2021 ◽

Author(s):

Lize Delanghe ◽

Irina Spacova ◽

Joke Van Malderen ◽

Eline Oerlemans ◽

Ingmar Claes ◽

...

Keyword(s):

Clinical Trials ◽

Skin Diseases ◽

Skin Barrier Function ◽

Skin Microbiome ◽

Inflammatory Skin Diseases ◽

Cutibacterium Acnes ◽

Inflammatory Skin ◽

Skin Conditions

The human skin microbiota forms a key barrier against skin pathogens and is important in modulating immune responses. Recent studies identify lactobacilli as endogenous inhabitants of healthy skin, while inflammatory skin conditions are often associated with a disturbed skin microbiome. Consequently, lactobacilli-based probiotics are explored as a novel treatment of inflammatory skin conditions through their topical skin application. This review focuses on the potential beneficial role of lactobacilli (family Lactobacillaceae) in the skin habitat, where they can exert multifactorial local mechanisms of action against pathogens and inflammation. On one hand, lactobacilli have been shown to directly compete with skin pathogens through adhesion inhibition, production of antimicrobial metabolites, and by influencing pathogen metabolism. The competitive anti-pathogenic action of lactobacilli has already been described mechanistically for common different skin pathogens, such as Staphylococcus aureus, Cutibacterium acnes, and Candida albicans. On the other hand, lactobacilli also have an immunomodulatory capacity associated with a reduction in excessive skin inflammation. Their influence on the immune system is mediated by bacterial metabolites and cell wall-associated or excreted microbe-associated molecular patterns (MAMPs). In addition, lactobacilli can also enhance the skin barrier function, which is often disrupted as a result of infection or in inflammatory skin diseases. Some clinical trials have already translated these mechanistic insights into beneficial clinical outcomes, showing that topically applied lactobacilli can temporarily colonize the skin and promote skin health, but more and larger clinical trials are required to generate in vivo mechanistic insights and in-depth skin microbiome analysis.

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In Vivo Reflectance Confocal Microscopy for Inflammatory Skin Diseases’ Assessment

Non Invasive Diagnostic Techniques in Clinical Dermatology ◽

10.1007/978-3-642-32109-2_7 ◽

2013 ◽

pp. 73-79

Author(s):

Marco Ardigò ◽

Marina Agozzino ◽

Leonardo Abraham

Keyword(s):

Confocal Microscopy ◽

Skin Diseases ◽

Reflectance Confocal Microscopy ◽

Inflammatory Skin Diseases ◽

Inflammatory Skin

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AB0019 TREATMENT OF AUTOIMMUNE AND INFLAMMATORY SKIN DISEASES USING SKIN-TARGETING BIFUNCTIONAL ANTIBODIES: A LOCALIZED IMMUNOMODULATION APPROACH

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.1665 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1043.3-1044

Author(s):

S. Borthakur ◽

P. Mande ◽

D. Rios ◽

P. Halvey ◽

A. Boisvert ◽

...

Keyword(s):

T Cell Activation ◽

Immune Modulation ◽

Cell Activation ◽

Skin Diseases ◽

Contact Hypersensitivity ◽

Inflammatory Skin Diseases ◽

Tissue Specific ◽

Inflammatory Skin

Background:Current treatment approaches for autoimmune conditions comprise primarily of systemic immunosuppressants or cytokine blockade. The concentration of therapeutic molecules to the tissues that are the sites of autoimmune and inflammatory diseases is a promising approach with the potential to induce therapeutic benefit and avert risks associated with systemic immunotherapies. Pandion Therapeutics is developing a bifunctional antibody platform that can drive localized immune modulation by combining a “tether antibody” that targets a tissue of choice and “an effector end” that activates specific regulatory immune pathways to restore immune-homeostasis.Objectives:Here we report the engineering of a skin-tethered PD-1 agonist and a skin-tethered CD39 that inhibit T cell activation and function and deplete local ATP, respectively, modulating different arms of the immune system in a tissue specific manner.Methods:Biophysical assays were performed to characterize Skin-tethered immune effectors for drug-like properties and in vitro and in vivo assays for target binding, cellular activity and tissue specific-localization. Moreover, these bifunctionals were tested in pathway-relevant preclinical models such as Vitiligo and Contact Hypersensitivity.Results:Biophysical characterization of the bifunctional molecules showed desired drug like properties including specificity, stability, and manufacturability. The skin tethered bifunctionals showed effector activity in in vitro assays and selectively localized to the skin. Skin localization strikingly correlated with a tether-dependent efficacy compared to a non-tether control.Conclusion:We believe that this therapeutic approach has the potential to drive the resolution of cutaneous inflammation, providing an opportunity for developing new targeted therapies for autoimmune and inflammatory skin diseases.Disclosure of Interests:Susmita Borthakur Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion therapeutics Inc., Purvi Mande: None declared, Daniel Rios: None declared, Patrick Halvey: None declared, Angela Boisvert: None declared, MIchael Rowe: None declared, Anisha Agrawal: None declared, Minasri Borah: None declared, Mike Cianci: None declared, Joanne L. Viney Shareholder of: Pandion therapeutics Inc., Consultant of: Harpoon, Finch, Quench, HotSpot, Employee of: Pandion Therapeutics Inc., Katalin Kis-Toth: None declared, Kevin L. Otipoby Shareholder of: Pandion Therapeutics Inc., Employee of: Pandion Therapeutics Inc., Ivan Mascanfroni: None declared, Nathan Higginson-Scott Shareholder of: Pandion Therapeutics Inc., Consultant of: Mediar Tx, Employee of: Pandion Therapeutics Inc.

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