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      Effects of Fisetin on Allergic Contact Dermatitis via Regulating the Balance of Th17/Treg in Mice

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          Abstract

          Background

          Allergic contact dermatitis (ACD) is a form of chronic cutaneous inflammatory disease of immunological origin that has adverse impacts on patient quality of life, underscoring the need for the development of safe and effective therapeutic agents to treat affected individuals. Fisetin is a Chinese herbal preparation that reportedly exhibits antitumor, antioxidant, antimicrobial, anticoagulatory, and antimalarial activity. In the current report, the immunomodulatory activity of fisetin was appraised by assessing its impact on balance between regulatory T (Treg) and Th17 cells in an ACD model.

          Methods

          BALB/c mice ( n = 60) were randomized into control, ACD model, CTX positive control (20 mg/kg), and fisetin treatment groups (three dose levels: 2, 4, or 8 mg/kg). ACD induction was achieved by sensitizing mice on the shaved ventral abdomen via the application of 5% DNFB (50  μL) on days 1 and 2, followed by rechallenge in the right ear with 5% DNFB (20  μL) on day 5. Beginning on day 1, immunized mice were intraperitoneally injected with the appropriate fisetin dose (in saline) once per day for 7 days. On day 7, ear swelling, transcription factor expression, Th17/Treg cell populations, and cytokine production were assessed in vivo.

          Results

          Fisetin treatment significantly suppressed ear swelling and associated inflammatory cell infiltration, besides reducing the production of Th17 cytokines (IL-17, TNF- α, and IL-6) and the expression of the Th17 lineage transcription factor ROR γt while simultaneously enhancing Treg-specific cytokine production (TGF- β and IL-10) and the expression of the Treg lineage transcription factor Foxp3, thereby restoring the Th17/Treg cell in ACD mice.

          Conclusions

          These data indicate that fisetin exhibits immunomodulatory activity and can alter the Th17/Treg cell balance, highlighting its potential value as a treatment drug for ACD.

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          Most cited references44

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          B cell regulation in cancer and anti-tumor immunity

          The balance between immune effector cells and immunosuppressive cells and how this regulates the tumor microenvironment has been well described. A significant contribution of immune regulatory cells, including regulatory T cells, to tumor progression has been widely reported. An emerging body of evidence has recently recognized a role for B cells in modulating the immune response to tumors and lymphoid malignancies. Regulatory B cells (Bregs) are a newly designated subset of B cells that have been shown to play a pivotal role in regulating immune responses involved in inflammation, autoimmunity and, more recently, cancer. Bregs can suppress diverse cell subtypes, including T cells, through the secretion of anti-inflammatory mediators, such as IL-10, and can facilitate the conversion of T cells to regulatory T cells, thus attenuating anti-tumor immune responses. Similar B-cell subpopulations have been reported to be recruited to the tumor but to acquire their immunosuppressive properties within the tumor bed and thereby attenuate anti-tumor immune responses. However, despite a pivotal role for Bregs in promoting inflammation and carcinogenesis, the phenotypic diversity of the cell surface markers that are unique to Bregs remains unclear in mice and humans. In this review, we summarize the characteristics of Bregs and review our current knowledge of Bregs and their inhibition of anti-tumor immune responses in murine tumor models and cancer patients.
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            When worlds collide: Th17 and Treg cells in cancer and autoimmunity

            The balance between Th17 cells and regulatory T cells (Tregs) has emerged as a prominent factor in regulating autoimmunity and cancer. Th17 cells are vital for host defense against pathogens but have also been implicated in causing autoimmune disorders and cancer, though their role in carcinogenesis is less well understood. Tregs are required for self-tolerance and defense against autoimmunity and often correlate with cancer progression. This review addresses the importance of a functional homeostasis between these two subsets in health and the consequences of its disruption when these forces collide in disease. Importantly, we discuss the ability of Th17 cells to mediate cancer regression in immunotherapy, including adoptive transfer and checkpoint blockade therapy, and the therapeutic possibilities of purposefully offsetting the Th17/Treg balance to treat patients with cancer as well as those with autoimmune diseases.
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              Comorbidities and the impact of atopic dermatitis

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                Author and article information

                Contributors
                Journal
                Comput Math Methods Med
                Comput Math Methods Med
                cmmm
                Computational and Mathematical Methods in Medicine
                Hindawi
                1748-670X
                1748-6718
                2022
                9 April 2022
                : 2022
                : 9222541
                Affiliations
                1Department of Pharmaceutical Engineering, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang Province, China
                2Molecular Mechanism of Disease & Research and Development of Bioactive Substances, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang Province, China
                3Animal Husbandry and Veterinary Station of Yongji Economic Development Zone, Jilin, 132200 Jilin Province, China
                4Department of Biological Engineering, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang Province, China
                5Department of Biological Science, College of Life Science & Technology, Heilongjiang Bayi Agricultural University, Daqing, 163319 Heilongjiang Province, China
                Author notes

                Academic Editor: Min Tang

                Author information
                https://orcid.org/0000-0003-3532-2950
                https://orcid.org/0000-0003-4258-3235
                https://orcid.org/0000-0001-8637-8650
                https://orcid.org/0000-0001-8794-8299
                https://orcid.org/0000-0002-3651-0091
                https://orcid.org/0000-0003-4460-8424
                https://orcid.org/0000-0003-3118-946X
                https://orcid.org/0000-0002-5608-6718
                https://orcid.org/0000-0002-2132-7980
                https://orcid.org/0000-0002-4392-5041
                https://orcid.org/0000-0003-4495-5864
                Article
                10.1155/2022/9222541
                9013294
                35437448
                c5cc99da-12d3-4b6e-aae0-e0fa919159ab
                Copyright © 2022 Bocui Song et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 February 2022
                : 16 March 2022
                : 21 March 2022
                Funding
                Funded by: College Students' Innovation and Entrepreneurship Training Program in Heilongjiang Province: Inhibitory Effect of Gossypol on Eotaxin in IgE Mediated Type I Allergic Reaction Mice
                Award ID: 201910223026
                Funded by: Training Program for Youth Innovation Talents of Heilongjiang Educational Committee
                Award ID: UNPYSCT-2017
                Funded by: Heilongjiang Bayi Agricultural University
                Award ID: TDJH201905
                Award ID: XYB2015-09
                Funded by: Postdoctoral Scientific Research Start-up Fund of Heilongjiang
                Award ID: LBH-Q21158
                Funded by: National Natural Science Foundation of China
                Award ID: 31772789
                Award ID: 31702289
                Categories
                Research Article

                Applied mathematics
                Applied mathematics

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