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      Fucoxanthin Ameliorates Atopic Dermatitis Symptoms by Regulating Keratinocytes and Regulatory Innate Lymphoid Cells

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          Abstract

          Fucoxanthin (FX) is a xanthophyll that is contained abundantly in marine plants. The biological action of FX includes its antioxidant and anti-lipogenic activities, while the precise action of its mechanisms on skin cells has not yet been clarified. The current study examined the effect of FX in comparison with tacrolimus (TAC) on NC/Nga mice, which are an atopic dermatitis (AD) model. FX topical treatment dramatically ameliorated itching behavior over the TAC treatment, which was insufficient for improvement of AD symptoms. In Nc/Nga mice, FX or TAC applied to the skin inhibited eosinophil infiltration with decreased expression of Il-33. FX also stimulated Il-2, Il-5, Il-13, Il-10, and TGF-β expression levels, and Sca1 +Il-10 +TGF-β + regulatory innate lymphoid cells (ILCreg) were dominantly observed in FX treated skin epidermal keratinocytes and dermal layers. This combined evidence demonstrated that FX exerts anti-inflammatory effects on keratinocytes and ameliorates AD symptoms by regulating ILCreg to normalize immune responses in an atopic dermatitis model.

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          Most cited references42

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          Regulatory T Cells in Skin Facilitate Epithelial Stem Cell Differentiation

          The maintenance of tissue homeostasis is critically dependent on the function of tissue-resident immune cells and the differentiation capacity of tissue-resident stem cells (SCs). How immune cells influence the function of SCs is largely unknown. Regulatory T cells (Tregs) in skin preferentially localize to hair follicles (HFs), which house a major subset of skin SCs (HFSCs). Here, we mechanistically dissect the role of Tregs in HF and HFSC biology. Lineage-specific cell depletion revealed that Tregs promote HF regeneration by augmenting HFSC proliferation and differentiation. Transcriptional and phenotypic profiling of T regs and HFSCs revealed that skin-resident Tregs preferentially express high levels of the Notch ligand family member, Jagged 1 (Jag1). Expression of Jag1 on Tregs facilitated HFSC function and efficient HF regeneration. Taken together, our work demonstrates that Tregs in skin play a major role in HF biology by promoting the function of HFSCs.
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            Th2 Cytokines and Atopic Dermatitis.

            Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease, is increasing in prevalence around the world. Intensive research is ongoing to understand the mechanisms involved in the development of AD and offer new treatment options for patients suffering from AD. In this review, we highlight the importance of allergic Th2 responses in the development of the disease and summarize relevant literature, including genetic studies, studies of human skin and mechanistic studies on keratinocytes and mouse models of AD. We discuss the importance of the skin barrier and review recent findings on the pro-Th2 cytokines TSLP, IL-25, and IL-33, notably their ability to polarize dendritic cells and promote Th2 responses. After a brief update on the contribution of different T-cell subsets to AD, we focus on Th2 cells and the respective contributions of each of the Th2 cytokines (IL-4, IL-13, IL-5, IL-31, and IL-10) to AD. We conclude with a brief discussion of the current gaps in our knowledge and technical limitations.
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              Transforming growth factor beta 1 null mutation in mice causes excessive inflammatory response and early death.

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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                22 March 2020
                March 2020
                : 21
                : 6
                : 2180
                Affiliations
                [1 ]Molecular Toxicology Lab., Ritsumeikan University, Shiga 525-8577, Japan; chika.ntsm@ 123456gmail.com (C.N.); ph0075eh@ 123456ed.ritsumei.ac.jp (N.A.); 723tomoko@ 123456gmail.com (T.A.); casebykeisuke84@ 123456yahoo.co.jp (K.S.); sb0006vi@ 123456gmail.com (M.M.); ph0091fv@ 123456ed.ritsumei.ac.jp (A.I.); ko.tanaka@ 123456kobayashi.co.jp (K.T.)
                [2 ]Laboratory of Veterinary Pharmacology, Division of Veterinary Science, Osaka Prefecture University, Graduate School of Life and Environmental Science, Izumisano, Osaka 598-8531, Japan; azuma@ 123456vet.osakafu-u.ac.jp
                Author notes
                [* ]Correspondence: fujitat@ 123456fc.ritsumei.ac.jp ; Tel.: +81-77-561-2848
                [†]

                These authors contributed equally to this work.

                Article
                ijms-21-02180
                10.3390/ijms21062180
                7139773
                32235696
                5f2f3769-30d1-41d9-b1a3-e70b32dc204d
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 February 2020
                : 20 March 2020
                Categories
                Article

                Molecular biology
                fucoxanthin,tacrolimus,atopic dermatitis,keratinocytes,eosinophil,gata transcription factors,il-2,il-10,tgf-β,mast cells,ilcreg,ilc2

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