Pemphigus is considered an autoimmune bullous skin disorder associated with IgG against the desmosomal components, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1). This concept is supported by the in vitro and in vivo pathogenicity of anti-Dsg3/Dsg1 IgG and the mucosal blistering phenotype of mice with a genetic deficiency of Dsg3. Mice deficient for another desmosomal adhesion molecule, desmocollin 3 (Dsc3), show a similar pemphigus phenotype, and we investigated the pathogenicity of Dsc3-reactive IgG autoantibodies that were identified previously in a subset of patients with atypical pemphigus. We here demonstrate that IgG against Dsc3 causes loss of adhesion of epidermal keratinocytes. Specifically, IgG against Dsc3 was purified from Dsc3-reactive pemphigus sera by affinity column chromatography using recombinant human Dsc3. Affinity purified IgG was functionally active and did not only react with recombinant Dsc3 but also with epidermis and cultured human keratinocytes. Moreover, Dsc3-reactive IgG induced loss of adhesion of epidermal keratinocytes in a dispase-based keratinocyte dissociation assay that was reversed on pre-adsorption with human Dsc3 but not Dsg3. These findings demonstrate that IgG autoantibodies against an additional component of the desmosomes, Dsc3, induce loss of keratinocyte adhesion and thus may contribute to blister formation in pemphigus.
REFERENCESCarroll JM, McElwee KJ, King LE Jr et al. (2002) Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans. J Invest Dermatol 119:392-402 Fraticelli P, Sironi M, Bianchi G et al. (2001) Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J Clin Invest 107:1173-81 Freyschmidt-Paul P, McElwee KJ, Hoffmann R et al. (2006) Interferon-gamma-deficient mice are resistant to the development of alopecia areata. Br J Dermatol 155:515-21 Ghoreishi M, Martinka M, Dutz JP (2010) Type 1 interferon signature in the scalp lesions of alopecia areata. Br J Dermatol 163:57-62 Groom JR, Luster AD (2011) CXCR3 ligands: redundant, collaborative and antagonistic functions. Immunol Cell Biol 89:207-15 Hancock WW, Lu B, Gao W et al. (2000) Requirement of the chemokine receptor CXCR3 for acute allograft rejection. J Exp Med 192:1515-20 Ito T, Ito N, Bettermann A et al. (2004) Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model. Am J Pathol 164: 623-34 McElwee KJ, Boggess D, King LE Jr et al. (1998) Experimental induction of alopecia areatalike hair loss in C3H/HeJ mice using full-thickness skin grafts. J Invest Dermatol 111:797-803 McElwee KJ, Freyschmidt-Paul P, Sundberg JP et al. (2003) The pathogenesis of alopecia areata in rodent models. J Investig Dermatol Symp Proc 8:6-11 Paus R, Christoph T, Muller-Rover S (1999) Immunology of the hair follicle: a short journey into terra incognita. J Investig Dermatol Symp Proc 4:226-34
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.