Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

Fetter, Tanja; Niebel, Dennis; Braegelmann, Christine; Wenzel, Joerg

doi:10.3390/cells9122627

Cited by 36 publications

(27 citation statements)

References 257 publications

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“… Illustration of the B-cell presence in the SSc patients skin (adapted from Fetter et al. Cells, 2020 [ 13 )]. CD20 + B-cells and plasma cells infiltrate the skin of SSc patients, from the early stages of the disease, especially around blood vessels, accompanied by other peripheral blood mononuclear cells, such as CD3 + T cells or follicular dendritic cells.…”

Section: B-cells Are Found In Affected Organsmentioning

confidence: 99%

Role of B-Cell in the Pathogenesis of Systemic Sclerosis

2022

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Systemic sclerosis (SSc) is a rare multisystem autoimmune disease, characterized by fibrosis, vasculopathy, and autoimmunity. Recent advances have highlighted the significant implications of B-cells in SSc. B-cells are present in affected organs, their subpopulations are disrupted, and they display an activated phenotype, and the regulatory capacities of B-cells are impaired, as illustrated by the decrease in the IL-10+ producing B-cell subpopulation or the inhibitory membrane co-receptor density. Recent multi-omics evidence highlights the role of B-cells mainly in the early stage of SSc and preferentially during severe organ involvement. This dysregulated homeostasis partly explains the synthesis of anti-endothelial cell autoantibodies (AECAs) or anti-fibroblast autoantibodies (AFAs), proinflammatory or profibrotic cytokines (interleukin-6 and transforming growth factor-β) produced by B and plasma cells. That is associated with cell-to-cell interactions with endothelial cells, fibroblasts, vascular smooth muscle cells, and other immune cells, altogether leading to cell activation and proliferation, cell resistance to apoptosis, the impairment of regulatory mechanisms, and causing fibrosis of several organs encountered in the SSc. Finally, alongside these exploratory data, treatments targeting B-cells, through their depletion by cytotoxicity (anti-CD20 monoclonal antibody), or the cytokines produced by the B-cell, or their costimulation molecules, seem interesting, probably in certain profiles of early patients with severe organic damage.

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Section: B-cells Are Found In Affected Organsmentioning

confidence: 99%

Role of B-Cell in the Pathogenesis of Systemic Sclerosis

2022

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“…6 Several autoimmune skin diseases are positively correlated with the infiltrating B-cell subsets. [6][7][8][9] Moreover, the skin-homing B-cells respond to local antigens and produce antibodies, which is devoid of primary and secondary lymphoid organs. These antibodies play a crucial role in autoimmune diseases.…”

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confidence: 99%

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Zaid¹,

Sekar²,

Bonam³

et al. 2022

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The skin is the largest organ in the human body, composed of the epidermis and the dermis. It provides protection and acts as a barrier against external menaces like allergens, chemicals, systemic toxicity, and infectious organisms. Skin disorders like cancer, dermatitis, psoriasis, wounds, skin aging, acne, and skin infection occur frequently and can impact human life. According to a growing body of evidence, several studies have reported that natural products have the potential for treating skin disorders. Building on this information, this review provides brief information about the action of the most important in vitro and in vivo research on the use of ten selected natural products in inflammatory, neoplastic, and infectious skin disorders and their mechanisms that have been reported to date. The related studies and articles were searched from several databases, including PubMed, Google, Google Scholar, and ScienceDirect. Ten natural products that have been reported widely on skin disorders were reviewed in this study, with most showing anti-inflammatory, antioxidant, anti-microbial, and anti-cancer effects as the main therapeutic actions. Overall, most of the natural products reported in this review can reduce and suppress inflammatory markers, like tumor necrosis factor-alpha (TNF-α), scavenge reactive oxygen species (ROS), induce cancer cell death through apoptosis, and prevent bacteria, fungal, and virus infections indicating their potentials. This review also highlighted the challenges and opportunities of natural products in transdermal/topical delivery systems and their safety considerations for skin disorders. Our findings indicated that natural products might be a low-cost, welltolerated, and safe treatment for skin diseases. However, a larger number of clinical trials are required to validate these findings. Natural products in combination with modern drugs, as well as the development of novel delivery mechanisms, represent a very promising area for future drug discovery of these natural leads against skin disorders.

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“…Further, they can be a source of autoreactive antibodies. However, they can also be negative regulators of the immune system, especially during inflammation and autoimmunity and specific B cell subsets, so called regulatory B cells, have been reported [ 37 , 38 , 39 , 40 , 41 ]. These regulatory B cells have been identified regularly in mouse models for inflammation and autoimmunity, where several subsets of these cells have been acknowledged [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Radon Improves Clinical Response in an Animal Model of Rheumatoid Arthritis Accompanied by Increased Numbers of Peripheral Blood B Cells and Interleukin-5 Concentration

Deloch

Hehlgans

Rückert

et al. 2022

Cells

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Radon treatment is used as an established therapy option in chronic painful inflammatory diseases. While analgesic effects are well described, little is known about the underlying molecular effects. Among the suspected mechanisms are modulations of the anti-oxidative and the immune system. Therefore, we aimed for the first time to examine the beneficial effects of radon exposure on clinical outcome as well as the underlying mechanisms by utilizing a holistic approach in a controlled environment of a radon chamber with an animal model: K/BxN serum-induced arthritic mice as well as isolated cells were exposed to sham or radon irradiation. The effects on the anti-oxidative and the immune system were analyzed by flow-cytometry, qPCR or ELISA. We found a significantly improved clinical disease progression score in the mice, alongside significant increase of peripheral blood B cells and IL-5. No significant alterations were visible in the anti-oxidative system or regarding cell death. We conclude that neither cell death nor anti-oxidative systems are responsible for the beneficial effects of radon exposure in our preclinical model. Rather, radon slightly affects the immune system. However, more research is still needed in order to fully understand radon-mediated effects and to carry out reasonable risk-benefit considerations.

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Skin-Associated B Cells in the Pathogenesis of Cutaneous Autoimmune Diseases—Implications for Therapeutic Approaches

Cited by 36 publications

References 257 publications

Role of B-Cell in the Pathogenesis of Systemic Sclerosis

Role of B-Cell in the Pathogenesis of Systemic Sclerosis

Promising Natural Products in New Drug Design, Development, and Therapy for Skin Disorders: An Overview of Scientific Evidence and Understanding Their Mechanism of Action

Radon Improves Clinical Response in an Animal Model of Rheumatoid Arthritis Accompanied by Increased Numbers of Peripheral Blood B Cells and Interleukin-5 Concentration

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