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3'-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models.

ABSTRACT: 3'-Sialyllactose (3'-SL), a natural prebiotic, maintains immune homeostasis and exerts anti-inflammatory and anti-arthritic effects. Although regulatory T cells (Tregs) prevent excessive inflammation and maintain immune tolerance, the effect of 3'-SL on Treg regulation is unclear. This study aimed to investigate the effect of 3'-SL on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3'-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeated topical application of house dust mites (HDM) and 2,4-dinitrochlorobenzene (DNCB). 3'-SL inhibited IgE, IL-1?, IL-6, and TNF-? secretion and markedly downregulated AD-related cytokines including IL-4, IL-5, IL-6, IL-13, IL-17, IFN-?, TNF-?, and Tslp through regulation of NF-?B in ear tissue. Additionally, in vitro assessment of Treg differentiation revealed that 3'-SL directly induced TGF-?-mediated Treg differentiation. Furthermore, 3'-SL administration also ameliorated sensitization and elicitation of AD pathogenesis by suppressing mast cell infiltration and production of IgE and pro-inflammatory cytokines in mouse serum by mediating the Treg response. Furthermore, Bifidobacterium population was also increased by 3'-SL administration as prebiotics. Our data collectively show that 3'-SL has therapeutic effects against AD progression by inducing Treg differentiation, downregulating AD-related cytokines, and increasing the Bifidobacterium population.

SUBMITTER: Kang LJ

PROVIDER: S-EPMC7101440 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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3'-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models.

Kang Li-Jung LJ Oh Eunjeong E Cho Chanmi C Kwon HoKeun H Lee Choong-Gu CG Jeon Jimin J Lee Hyemi H Choi Sangil S Han Seong Jae SJ Nam Jiho J Song Chi-Une CU Jung Hyunho H Kim Hye Young HY Park Eun-Jung EJ Choi Eun-Ju EJ Kim Jooyoung J Eyun Seong-Il SI Yang Siyoung S

Scientific reports 20200327 1

3'-Sialyllactose (3'-SL), a natural prebiotic, maintains immune homeostasis and exerts anti-inflammatory and anti-arthritic effects. Although regulatory T cells (Tregs) prevent excessive inflammation and maintain immune tolerance, the effect of 3'-SL on Treg regulation is unclear. This study aimed to investigate the effect of 3'-SL on Treg responses in atopic dermatitis (AD) pathogenesis. Oral administration of 3'-SL reduced AD-like symptoms such as ear, epidermal, and dermal thickness in repeat ...[more]

PMID: 32221370

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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

3'-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models.

Publications

3'-Sialyllactose prebiotics prevents skin inflammation via regulatory T cell differentiation in atopic dermatitis mouse models.

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