Solidagenone from
            Solidago chilensis
            Meyen inhibits skin inflammation in experimental models

Dermatophytoses (ringworms) are among the most frequent skin infections and are a highly prevalent cause of human disease worldwide. Despite the incidence of these superficial mycoses in healthy people and the compelling evidence on chronic and deep infections in immunocompromised individuals, the mechanisms controlling dermatophyte invasion in the skin are scarcely known. In the last years, the association between certain primary immunodeficiencies and the susceptibility to severe dermatophytosis as well as the evidence provided by novel experimental models mimicking human disease have significantly contributed to deciphering the basic immunological mechanisms against dermatophytes. In this review, we outline the current knowledge on fungal virulence factors involved in the pathogenesis of dermatophytoses and recent evidence from human infections and experimental models that shed light on the cells and molecules involved in the antifungal cutaneous immune response. The latest highlights emphasize the contribution of C-type lectin receptors signaling and the cellular immune response mediated by IL-17 and IFN-γ in the anti-dermatophytic defense and skin inflammation control.

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Keratinocytes control skin immune homeostasis through de novo–synthesized glucocorticoids

Science Advances ◽

10.1126/sciadv.abe0337 ◽

2021 ◽

Vol 7 (5) ◽

pp. eabe0337

Author(s):

Truong San Phan ◽

Leonhard Schink ◽

Jasmin Mann ◽

Verena M. Merk ◽

Pascale Zwicky ◽

...

Keyword(s):

T Cells ◽

De Novo ◽

Skin Inflammation ◽

Experimental Models ◽

Contact Hypersensitivity ◽

Skin Disorders ◽

Hydroxylase Deficiency ◽

Skin Immune System ◽

Inflammatory Skin

Glucocorticoids (GC), synthesized by the 11β-hydroxylase (Cyp11b1), control excessive inflammation through immunosuppressive actions. The skin was proposed to regulate homeostasis by autonomous GC production in keratinocytes. However, their immunosuppressive capacity and clinical relevance remain unexplored. Here, we demonstrate the potential of skin-derived GC and their role in the regulation of physiological and prevalent inflammatory skin conditions. In line with 11β-hydroxylase deficiency in human inflammatory skin disorders, genetic in vivo Cyp11b1 ablation and long-term GC deficiency in keratinocytes primed the murine skin immune system resulting in spontaneous skin inflammation. Deficient skin GC in experimental models for inflammatory skin disorders led to exacerbated contact hypersensitivity and psoriasiform skin inflammation accompanied by decreased regulatory T cells and the involvement of unconventional T cells. Our findings provide insights on how skin homeostasis and pathology are critically regulated by keratinocyte-derived GC, emphasizing the immunoregulatory potential of endogenous GC in the regulation of epithelial immune microenvironment.

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Experimental models of skin inflammation

Clinical & Experimental Allergy ◽

10.1046/j.1365-2222.1999.0290s3105.x ◽

1999 ◽

Vol 29 ◽

pp. 105-108 ◽

Cited By ~ 3

Author(s):

G. Clough

Keyword(s):

Skin Inflammation ◽

Experimental Models

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Molecular mechanisms of leukocyte trafficking in T-cell-mediated skin inflammation: insights from intravital imaging

Expert Reviews in Molecular Medicine ◽

10.1017/s146239940900115x ◽

2009 ◽

Vol 11 ◽

Cited By ~ 27

Author(s):

James A. Deane ◽

Michael J. Hickey

Keyword(s):

T Cell ◽

Adhesion Molecules ◽

Molecular Mechanisms ◽

Skin Diseases ◽

Imaging Techniques ◽

Skin Inflammation ◽

Experimental Models ◽

Clinical Samples ◽

Inflammatory Skin Diseases ◽

Cell Recruitment

Infiltration of T cells is a key step in the pathogenesis of the inflammatory skin diseases atopic dermatitis, allergic contact dermatitis and psoriasis. Understanding the mechanisms of T cell recruitment to the skin is therefore of fundamental importance for the discovery and application of novel therapies for these conditions. Studies of both clinical samples and experimental models of skin inflammation have implicated specific adhesion molecules and chemokines in lymphocyte recruitment. In particular, recent studies using advanced in vivo imaging techniques have greatly increased our understanding of the kinetics and molecular basis of this process. In this review, we summarise the current understanding of the cellular immunology of antigen-driven dermal inflammation and the roles of adhesion molecules and chemokines. We focus on results obtained using intravital microscopy to examine the dermal microvasculature and interstitium to determine the mechanisms of T cell recruitment and migration in experimental models of T-cell-mediated skin inflammation.

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ACE2 as therapeutic agent

Clinical Science ◽

10.1042/cs20200570 ◽

2020 ◽

Vol 134 (19) ◽

pp. 2581-2595

Author(s):

Qiuhong Li ◽

Maria B. Grant ◽

Elaine M. Richards ◽

Mohan K. Raizada

Keyword(s):

Therapeutic Agent ◽

Renin Angiotensin System ◽

Peptide Hormone ◽

Experimental Models ◽

Electrolyte Balance ◽

Ang Ii ◽

Angiotensin Converting Enzyme 2 ◽

Beneficial Effects ◽

Overwhelming Evidence ◽

Future Challenges

Abstract The angiotensin-converting enzyme 2 (ACE2) has emerged as a critical regulator of the renin–angiotensin system (RAS), which plays important roles in cardiovascular homeostasis by regulating vascular tone, fluid and electrolyte balance. ACE2 functions as a carboxymonopeptidase hydrolyzing the cleavage of a single C-terminal residue from Angiotensin-II (Ang-II), the key peptide hormone of RAS, to form Angiotensin-(1-7) (Ang-(1-7)), which binds to the G-protein–coupled Mas receptor and activates signaling pathways that counteract the pathways activated by Ang-II. ACE2 is expressed in a variety of tissues and overwhelming evidence substantiates the beneficial effects of enhancing ACE2/Ang-(1-7)/Mas axis under many pathological conditions in these tissues in experimental models. This review will provide a succinct overview on current strategies to enhance ACE2 as therapeutic agent, and discuss limitations and future challenges. ACE2 also has other functions, such as acting as a co-factor for amino acid transport and being exploited by the severe acute respiratory syndrome coronaviruses (SARS-CoVs) as cellular entry receptor, the implications of these functions in development of ACE2-based therapeutics will also be discussed.

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