T cell autoimmunity and immune regulation to desmoglein 3, a pemphigus autoantigen

Abstract

Pemphigus is a life‐threatening autoimmune bullous disease mediated by anti‐desmoglein IgG autoantibodies. Pemphigus is mainly classified into three subtypes: pemphigus vulgaris, pemphigus foliaceus, and paraneoplastic pemphigus. The pathogenicity of autoantibodies has been extensively studied. Anti‐human CD20 antibody therapy targeting B cells emerged as a more effective treatment option compared to conventional therapy for patients with an intractable disease. On the other hand, autoreactive T cells are considered to be involved in the pathogenesis based on the test results of human leukocyte antigen association, autoreactive T cell detection, and cytokine profile analysis. Research on the role of T cells in pemphigus has continued to progress, including that on T follicular helper cells, which initiate molecular mechanisms involved in antibody production in B cells. Autoreactive T cell research in mice has highlighted the crucial roles of cellular autoimmunity and improved the understanding of its pathogenesis, especially in paraneoplastic pemphigus. The mouse research has helped elucidate novel regulatory mechanisms of autoreactive T cells, such as thymic tolerance to desmoglein 3 and the essential roles of regulatory T cells, Langerhans cells, and other molecules in peripheral tissues. This review focuses on the immunological aspects of autoreactive T cells in pemphigus by providing detailed information on various related topics.

Comparative Transcriptome Analysis Identifies Desmoglein-3 as a Potential Oncogene in Oral Cancer Cells

“…In general, these findings suggest a potential oncogenic role of DSG3 in oral SCC cells, as proposed previously [2,36,37]. Another interesting finding from this study is that DSG3 plays a significant role in MHC complex assembly and binding (GO:0002399, GO:0002501, GO:0002396, GO:0042613, GO:0042611), pointing to its involvement in immune regulation, as demonstrated in pemphigus autoimmune blistering disease [38][39][40].…”

Vom Tumor zur Epidermolyse: mehrfach metastasierter solitärer fibröser Tumor mit paraneoplastischem Pemphigus

“…Die Dysregulation des antitumoral wirkenden Immunsystems und die Epitopausbreitung ( epitope spreading ) können zur Antikörperproduktion beitragen. Autoreaktive T‐Zellen vermitteln Zytotoxizität, was histopathologisch und in In‐vivo ‐Experimenten nachweisbar ist 4 . Die Ätiopathologie der PNP lässt sich daher grob als molekulares Mimikry mit Störung der zentralen und peripheren Toleranz zusammenfassen 5 .…”

“…Autoreaktive T-Zellen vermitteln Zytotoxizität, was histopathologisch und in In-vivo-Experimenten nachweisbar ist. 4 Die Ätiopathologie der PNP lässt sich daher grob als molekulares Mimikry mit Störung der zentralen und peripheren Toleranz zusammenfassen. 5 In unserem Fall könnte eine Kraniotomie-induzierte Antigenexposition eine mögliche Erklärung für das Auftreten der PNP sein.…”

From mass to epidermolysis: a rare case of multiple metastatic solitary fibrous tumor with paraneoplastic pemphigus

“…Anti‐tumor immune dysregulation and epitope spreading may contribute to antibody production. Autoreactive T cells mediate cytotoxicity in clinical histopathology and in vivo experiments 4 . Thus, the etiopathology of PNP can be broadly summarized as molecular mimicry, the breakdown of central and peripheral tolerance 5 .…”

“…Autoreactive T cells mediate cytotoxicity in clinical histopathology and in vivo experiments. 4 Thus, the etiopathology of PNP can be broadly summarized as molecular mimicry, the breakdown of central and peripheral tolerance. 5 In our case, craniotomy-induced antigen exposure could be a possible explanation for the onset of PNP.…”