Editorial: Skin Autoimmunity

Abstract

Editorial on the Research Topic Skin Autoimmunity According to the revised Witebsky’s criteria by Rose and Bona, a disease is considered of autoimmune origin if (i) it can be transferred by pathogenic T cells or autoantibodies, (ii) it can be induced in experimental animals, or if (iii) autoimmunity is suggested by circumstantial evidence from clinical clues (1). Rather new aspects are the iatrogenic induction of autoimmune side effects or the emergence of cutaneous side effects by new immunomodulating therapies (2, 3). According to the “classical definition”, skin autoimmune diseases include pemphigus and pemphigoid diseases (4, 5). In pemphigus and pemphigoid, autoantibodies bind to specific structural proteins of the skin and either directly or indirectly (through activation of the immune system) induce skin pathology (6). Within this Research Topic, several review articles provide an excellent overview of several pemphigus and pemphigoid diseases. More specifically, paraneoplastic pemphigus, bullous pemphigoid, anti-p200 pemphigoid and lichen planus pemphigoides are reviewed in detail. Within this editorial, we aim to provide an overview of the 68 articles of the Research Topic. Each article of the Research Topic can be directly assessed by the kinks provided in the blue font. To guide the reading, we have classified the articles into the following subheadings: ● “Emerging” autoimmune diseases ● Novel insights into the pathogenesis of skin autoimmune diseases ● New diagnostic approaches in skin autoimmune diseases ● Comorbidity in skin autoimmune diseases ● Epidemiology of skin autoimmune diseases ● Novel treatment targets and therapeutic approaches for skin autoimmune diseases ● Characterization of patient biomaterials and model systems of skin autoimmune diseases In contrast to these more “classical” autoimmune diseases, fulfilling the revised Witebsky’s criteria, there is an increasing evidence for a role of autoreactive T- and/or B-cells in chronic inflammatory skin diseases that have not been considered autoimmune so far (7). As reviewed by Boehncke and Brembilla autoreactive T cells are present in several chronic skin inflammatory diseases that are (so far) not considered to be caused by an aberrant immune response to self-antigens. Among others, autoreactive T cells have been identified in psoriasis and atopic dermatitis (8–10). Overall, these are very intriguing findings, but before fully considering autoimmunity as a significant contributing factor to psoriasis or atopic dermatitis, these findings require functional validation. In addition to T cell-mediated autoimmunity in “non-autoimmune” chronic inflammatory skin diseases, presence of autoantibodies has been described in chronic spontaneous urticaria (CSU), as well as in morphea. Yet, again, these findings await functional validation in vivo. The induction of systemic sclerosis, which shares pathogenic features of morphea, in mice immunized with type V collagen (11), however, provides strong evidence for a pathogenic contribution of autoantibodies in morphea and/or systemic sclerosis. In light of the increasing importance of pathogenetic networks of innate and adaptive immune responses (12, 13), this and other observations are highlighted in the review by Schön, where in psoriasis and other autoimmune or autoinflammatory diseases, and their relation to disease pathogenies is highlighted. A complex interaction of genetics and environmental factors is one of the key underlying pathogenic mechanisms in skin autoimmune diseases. The high number of submissions reporting on genetic associations in autoimmune skin diseases underscores this. The genetics and transcriptomics in pemphigus and pemphigoid are reviewed by Olbrich et al. Targeted genetic analysis identified novel gene polymorphisms in endemic pemphigus foliaceus, namely within cell death pathways and the soluble CR1. While most genetic studies focus on the nuclear genome, few address the impact of the mitochondrial genome on complex phenotypes. This highly interesting topic has been addressed by Russlies et al., who report on polymorphisms in the mitochondrial genome that are associated with bullous pemphigoid. In addition to genetics, several articles also specifically address certain cell types in skin autoimmune diseases. Cao et al. allude to the role of regulatory immune cells in pemphigus and pemphigoid. Here, with a focus on pemphigus and pemphigoid, they review the impact of different types of regulatory T and B cells. Rauschenberger et al. present data on the crosstalk between skin infiltrating T cells and keratinocytes. Costa et al. focus on the contribution of mononuclear phagocyte activation in the context of psoriasis. Based on the determination of molecular markers of monocyte/phagocyte activation in inflamed skin and the serum of patients, they conclude that mononuclear phagocytes are activated in psoriasis and thus may contribute to disease pathogenesis. Interestingly, similar findings were made in patients with bullous pemphigoid by Riani et al. Neubert et al. also focus on the contribution of innate immune cells in the pathogenesis of chronic skin inflammation: Neutrophil extracellular traps (NETs) may be formed after neutrophil activation. NETs are important for host defense, but may also contribute to the pathogenesis of several chronic inflammatory (skin) diseases, such as rheumatoid arthritis, psoriasis, or systemic lupus erythematosus (SLE). Interestingly, some of these diseases may be triggered or aggravated by light exposure. Based on these findings, the authors investigated the impact of UVA on NET formation. Another set of articles within the Research Topic focus on the role of cytokines in the pathogenesis of chronic skin inflammation: Buhl and Wenzel highlight the importance of...