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Lactobacillus sakei WIKIM30 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Regulatory T Cells and Altering Gut Microbiota Structure in Mice.

ABSTRACT: Lactobacillus sakei WIKIM30 is a Gram-positive facultative anaerobic bacterium isolated from kimchi, a Korean fermented vegetable food. In this study, we found that WIKIM30 promoted regulatory T cell (Treg) differentiation by inducing dendritic cells with tolerogenic properties. The production of the T helper (Th) 2-associated cytokine interleukin (IL)-4 was decreased, but that of the Treg-associated cytokine IL-10 was increased in splenocytes from ovalbumin-sensitized mice treated with WIKIM30. We also investigated the inhibitory capacity of WIKIM30 on the development of 2,4-dinitrochlorobenzene-induced atopic dermatitis (AD), a Th2-dominant allergic disease in mice. Oral administration of L. sakei WIKIM30 significantly reduced AD-like skin lesions and serum immunoglobulin E and IL-4 levels while decreasing the number of CD4⁺ T cells and B cells and the levels of Th2 cytokines (IL-4, IL-5, and IL-13) in peripheral lymph nodes and enhancing Treg differentiation and IL-10 secretion in mesenteric lymph nodes. In addition, WIKIM30 modulated gut microbiome profiles that were altered in AD mice, which showed increases in Arthromitus and Ralstonia and a decrease in Ruminococcus abundance. These changes were reversed by WIKIM30 treatment. Notably, the increase in Ruminococcus was highly correlated with Treg-related responses and may contribute to the alleviation of AD responses. Together, these results suggest that oral administration of L. sakei WIKIM30 modulates allergic Th2 responses enhancing Treg generation and increases the relative abundance of intestinal bacteria that are positively related to Treg generation, and therefore has therapeutic potential for the treatment of AD.

SUBMITTER: Kwon MS

PROVIDER: S-EPMC6102352 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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<i>Lactobacillus sakei</i> WIKIM30 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Regulatory T Cells and Altering Gut Microbiota Structure in Mice.

Kwon Min-Sung MS Lim Seul Ki SK Jang Ja-Young JY Lee Jieun J Park Hyo Kyeong HK Kim Namhee N Yun Misun M Shin Mi-Young MY Jo Hee Eun HE Oh Young Joon YJ Roh Seong Woon SW Choi Hak-Jong HJ

Frontiers in immunology 20180814

<i>Lactobacillus sakei</i> WIKIM30 is a Gram-positive facultative anaerobic bacterium isolated from kimchi, a Korean fermented vegetable food. In this study, we found that WIKIM30 promoted regulatory T cell (Treg) differentiation by inducing dendritic cells with tolerogenic properties. The production of the T helper (Th) 2-associated cytokine interleukin (IL)-4 was decreased, but that of the Treg-associated cytokine IL-10 was increased in splenocytes from ovalbumin-sensitized mice treated with W ...[more]

PMID: 30154801

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Project description:Atopic dermatitis (AD), also known as atopic eczema, is one of the most common skin diseases and is characterized by allergic skin inflammation, redness, and itchiness and is associated with a hyperactivated type 2 immune response. The leading causes of AD include an imbalance in the immune system, genetic predisposition, or environmental factors, making the development of effective pharmacotherapies complex. Steroids are widely used to treat AD; however, they provide limited efficacy in the long term and can lead to adverse effects. Thus, novel treatments that offer durable efficacy and fewer side effects are urgently needed. Here, we investigated the therapeutic potential of Huangbai Liniment (HB), a traditional Chinese medicine, using an experimental AD mouse model, following our clinical observations of AD patients. In both AD patient and the mouse disease model, HB significantly improved the disease condition. Specifically, patients who received HB treatment on local skin lesions (3-4 times/day) showed improved resolution of inflammation. Using the 1-Chloro-2,4-dinitrobenzene (DNCB)-induced AD model in BALB/c mice, we observed that HB profoundly alleviated severe skin inflammation and relieved the itching. The dermatopathological results showed markedly reversed skin inflammation with decreased epidermal thickness and overall cellularity. Correspondingly, HB treatment largely decreased the mRNA expression of proinflammatory cytokines, including IL-1β, TNF-α, IL-17, IL-4, and IL-13, associated with declined gene expression of IL-33, ST2, and GATA3, which are connected to the type 2 immune response. In addition, HB restored immune tolerance by promoting regulatory T (TREG) cells and inhibiting the generation of TH1, TH2, and TH17 cells in vitro and in the DNCB-induced AD mouse model. For the first time, we demonstrate that HB markedly mitigates skin inflammation in AD patients and the DNCB-induced AD mouse model by reinvigorating the T cell immune balance, shedding light on the future development and application of novel HB-based therapeutics for AD.

Dataset Information

Lactobacillus sakei WIKIM30 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Regulatory T Cells and Altering Gut Microbiota Structure in Mice.

Publications

<i>Lactobacillus sakei</i> WIKIM30 Ameliorates Atopic Dermatitis-Like Skin Lesions by Inducing Regulatory T Cells and Altering Gut Microbiota Structure in Mice.

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