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Autoimmune and infectious skin diseases that target desmogleins.

Amagai M - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Bottom Line: Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia.Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development.Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. amagai@sc.itc.keio.ac.jp

ABSTRACT
Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell-cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1-Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3(-/-) lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects.

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Clinical pictures of pemphigus patients. A. Oral erosions in a patient with pemphigus vulgaris. B. Heavily clotted and crusted lesions around the mouth in a patient with paraneoplastic pemphigus. C. Skin lesions found on the trunk in a patient with pemphigus vulgaris. D. Skin lesions on the trunk in a patient with pemphigus foliaceus.
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fig02: Clinical pictures of pemphigus patients. A. Oral erosions in a patient with pemphigus vulgaris. B. Heavily clotted and crusted lesions around the mouth in a patient with paraneoplastic pemphigus. C. Skin lesions found on the trunk in a patient with pemphigus vulgaris. D. Skin lesions on the trunk in a patient with pemphigus foliaceus.

Mentions: All patients with pemphigus vulgaris show mucous membrane lesions, which are usually seen as painful erosions (Fig. 2A). Intact blisters are rare, probably because they are fragile and break easily. Extensive erosions and painful lesions in the mouth may result in decreased food and drink intake. Involvement of the throat may produce hoarseness and difficulty in swallowing. The esophagus, conjunctiva, nasal mucosa, vagina, penis, anus, and labia may also be involved. The diagnosis of pemphigus vulgaris tends to be delayed in patients presenting with only oral involvement in comparison to those with skin lesions.


Autoimmune and infectious skin diseases that target desmogleins.

Amagai M - Proc. Jpn. Acad., Ser. B, Phys. Biol. Sci. (2010)

Clinical pictures of pemphigus patients. A. Oral erosions in a patient with pemphigus vulgaris. B. Heavily clotted and crusted lesions around the mouth in a patient with paraneoplastic pemphigus. C. Skin lesions found on the trunk in a patient with pemphigus vulgaris. D. Skin lesions on the trunk in a patient with pemphigus foliaceus.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3108298&req=5

fig02: Clinical pictures of pemphigus patients. A. Oral erosions in a patient with pemphigus vulgaris. B. Heavily clotted and crusted lesions around the mouth in a patient with paraneoplastic pemphigus. C. Skin lesions found on the trunk in a patient with pemphigus vulgaris. D. Skin lesions on the trunk in a patient with pemphigus foliaceus.
Mentions: All patients with pemphigus vulgaris show mucous membrane lesions, which are usually seen as painful erosions (Fig. 2A). Intact blisters are rare, probably because they are fragile and break easily. Extensive erosions and painful lesions in the mouth may result in decreased food and drink intake. Involvement of the throat may produce hoarseness and difficulty in swallowing. The esophagus, conjunctiva, nasal mucosa, vagina, penis, anus, and labia may also be involved. The diagnosis of pemphigus vulgaris tends to be delayed in patients presenting with only oral involvement in comparison to those with skin lesions.

Bottom Line: Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia.Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development.Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, Keio University School of Medicine, Tokyo, Japan. amagai@sc.itc.keio.ac.jp

ABSTRACT
Desmosomes are intercellular adhesive junctions of epithelial cells that contain two major transmembrane components, the desmogleins (Dsg) and desmocollins (Dsc), which are cadherin-type cell-cell adhesion molecules and are anchored to intermediate filaments of keratin through interactions with plakoglobin and desmoplakin. Desmosomes play an important role in maintaining the proper structure and barrier function of the epidermis and mucous epithelia. Four Dsg isoforms have been identified to date, Dsg1-Dsg4, and are involved in several skin and heart diseases. Dsg1 and Dsg3 are the two major Dsg isoforms in the skin and mucous membranes, and are targeted by IgG autoantibodies in pemphigus, an autoimmune disease of the skin and mucous membranes. Dsg1 is also targeted by exfoliative toxin (ET) released by Staphylococcus aureus in the infectious skin diseases bullous impetigo and staphylococcal scalded skin syndrome (SSSS). ET is a unique serine protease that shows lock and key specificity to Dsg1. Dsg2 is expressed in all tissues possessing desmosomes, including simple epithelia and myocardia, and mutations in this gene are responsible for arrhythmogenic right ventricular cardiomyopathy/dysplasia. Dsg4 plays an important adhesive role mainly in hair follicles, and Dsg4 mutations cause abnormal hair development. Recently, an active disease model for pemphigus was generated by a unique approach using autoantigen-deficient mice that do not acquire tolerance against the defective autoantigen. Adoptive transfer of Dsg3(-/-) lymphocytes into mice expressing Dsg3 induces stable anti-Dsg3 IgG production with development of the pemphigus phenotype. This mouse model is a valuable tool with which to investigate immunological mechanisms of harmful IgG autoantibody production in pemphigus. Further investigation of desmoglein molecules will continue to provide insight into the unsolved pathophysiological mechanisms of diseases and aid in the development of novel therapeutic strategies with minimal side effects.

Show MeSH
Related in: MedlinePlus