Epithelial barrier dysfunction in desmoglein-1 deficiency

Laura Polivka (1) , Smaïl Hadj-Rabia (2) , Elodie Bal (2) , Stéphanie Leclerc-Mercier (1) , Marine Madrange , Yamina Hamel (2) , Damien Bonnet (3) , Stéphanie Mallet (4) , Hubert Lepidi (5) , Caroline Ovaert (6) , Patrick Barbet , Christophe Dupont (7) , Bénédicte Neven (8) , Arnold Munnich (2) , Lisa M Godsel , Florence Campeotto (9) , Robert Weil (10) , Emmanuel Laplantine (10) , Sylvie Marchetto (11) , Jean-Paul Borg (11) , William I Weis , Jean-Laurent Casanova (2) , Anne Puel (12) , Kathleen Green (13) , Christine Bodemer (2) , Asma Smahi (2)

1 MAGEC - Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases
2 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
3 Hôpital Necker - Enfants Malades [AP-HP]
4 Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM]
5 MEPHI - Microbes évolution phylogénie et infections
6 Service de cardiologie Pédiatrique [Marseille]
7 LM-Orsay - Laboratoire de Mathématiques d'Orsay
8 Service d'immuno-hématologie pédiatrique [CHU Necker]
9 CHU Necker - Enfants Malades [AP-HP] - Gastro-Entérologie, Hépatologie et Nutrition pédiatriques
10 Signalisation et Pathogénèse
11 CRCM - Centre de Recherche en Cancérologie de Marseille
12 Inserm U980 - Génétique Humaine des Maladies Infectieuses
13 Department of Pathology

Mutations in the desmoplakin (DSP) and desmoglein-1 (DSG1) genes have been implicated in patients with the inherited inflammatory skin disease known as severe dermatitis, multiple allergies, and metabolic wasting (SAM) syndrome (MIM#603165, see Tables E1 and E2 in this article's Online Repository at www.jacionline.org).1, 2 The DSP and DSG1 genes encode desmosome components that are critical for the structure of intercellular junctions and maintenance of epithelial barrier integrity. DSP and DSG1 are also key regulators of signaling pathways involved in differentiation, epidermal homeostasis, and carcinogenesis. DSG1 promotes keratinocyte differentiation by inhibiting epidermal growth factor receptor/extracellular signal-regulated kinase signaling through ERBB2-interacting protein (ERBIN), a scaffolding and signaling protein.3 Through characterization of a new syndrome featuring severe allergic dermatitis and DSG1 deficiency, we highlighted the pivotal role of the functional DSG1/ERBIN interaction as an inhibitor of skin inflammation through the nuclear factor κB (NF-κB) signaling pathway.

Domaines: Biochimie, Biologie Moléculaire; Dermatologie; Pédiatrie

Laura Polivka, Smaïl Hadj-Rabia, Elodie Bal, Stéphanie Leclerc-Mercier, Marine Madrange, et al.. Epithelial barrier dysfunction in desmoglein-1 deficiency. Journal of Allergy and Clinical Immunology, 2018, 142 (2), pp.702-706.e7. ⟨10.1016/j.jaci.2018.04.007⟩. ⟨hal-02052255⟩