Experimental human cell and tissue models of pemphigus.

Gerda Van Der Wier,Marcel F Jonkman,Hendri H Pas

doi:10.1155/2010/143871

Gerda Van Der Wier, Marcel F Jonkman + Show 1 more

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https://doi.org/10.1155/2010/143871

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Abstract

Pemphigus is a chronic mucocutaneous autoimmune bullous disease that is characterized by loss of cell-cell contact in skin and/or mucous membranes. Past research has successfully identified desmosomes as immunological targets and has demonstrated that acantholysis is initiated through direct binding of IgG. The exact mechanisms of acantholysis, however, are still missing. Experimental model systems have contributed considerably to today's knowledge and are still a favourite tool of research. In this paper we will describe to what extent human cell and tissue models represent the in vivo situation, for example, organ cultures of human skin, keratinocyte cultures, and human skin grafted on mice and, furthermore, how suitable they are to study the pathogenesis of pemphigus. Organ cultures closely mimic the architecture of the epidermis but are less suitable to answer posed biochemical questions. Cultured keratinocyte monolayers are convenient in this respect, but their desmosomal make-up in terms of adhesion molecules does not exactly reflect the in vivo situation. Reconstituted skin is a relatively new model that approaches organ culture. In models of human skin grafted on mice, acantholysis can be studied in actual human skin but now with all the advantages of an animal model.

Highlights

Pemphigus is a chronic mucocutaneous autoimmune bullous disease, characterized by the presence of autoantibodies against the desmosomal cadherins, desmoglein 1 (Dsg1), and/or desmoglein 3 (Dsg3)
In the case of mucosal dominant pemphigus vulgaris (PV), patients have suprabasal blistering of the mucous membranes and auto-antibodies against Dsg3 only
Since the discovery by Beutner and Jordon in the sixties, who demonstrated by indirect immunofluorescence (IIF) microscopy that sera of pemphigus vulgaris patients contained Immunoglobulin G Fab (IgG) antibodies directed against a substance on the surface of keratinocytes [1], investigators have tried to answer an intriguing question: how do these antibodies cause acantholysis in skin? In the nineties, Mahoney et al presented their theories on steric hindrance and desmoglein compensation [2] as an explanation for acantholysis

Summary

Introduction

Pemphigus is a chronic mucocutaneous autoimmune bullous disease, characterized by the presence of autoantibodies against the desmosomal cadherins, desmoglein 1 (Dsg1), and/or desmoglein 3 (Dsg). PF presents as superficial blistering of the skin and the presence of autoantibodies against Dsg. Patients with mucocutaneous PV have suprabasal blistering of both the skin and the mucous membranes, in combination with autoantibodies against both Dsg and 3. Since the discovery by Beutner and Jordon in the sixties, who demonstrated by indirect immunofluorescence (IIF) microscopy that sera of pemphigus vulgaris patients contained IgG antibodies directed against a substance on the surface of keratinocytes [1], investigators have tried to answer an intriguing question: how do these antibodies cause acantholysis in skin? In this paper we will discuss the in vitro models and focus on human cell and tissue models. These models comprise organ cultures of human skin, cultured human monolayer keratinocytes, reconstituted skin, and human skin grafted on mice. We will discuss how well these human cell and tissue models represent the in vivo situation in human skin and their suitability to study the pathogenesis of pemphigus

Organ Cultures of Human Skin

Keratinocyte Cultures

Human Skin Grafted on Mice

Model Comparison