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

  • Sci Rep. 2020 Mar 27;10(1):5603. doi: 10.1038/s41598-020-62527-5.
Li-Jung Kang   #  1  2  3 Eunjeong Oh   #  1  2  3 Chanmi Cho  1  2  3 HoKeun Kwon  4 Choong-Gu Lee  5 Jimin Jeon  1  2  3 Hyemi Lee  1  2  3 Sangil Choi  1  2  3 Seong Jae Han  1  2  3 Jiho Nam  1  2  3 Chi-Une Song  6 Hyunho Jung  7 Hye Young Kim  3  8 Eun-Jung Park  9 Eun-Ju Choi  10 Jooyoung Kim  11 Seong-Il Eyun  12 Siyoung Yang  13  14  15
Affiliations
  • 1. Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea.
  • 2. Department of Pharmacology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea.
  • 3. CIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
  • 4. Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul, 03722, Korea.
  • 5. Korea Institute of Science & Technology (KIST) Gangneung Institute of Natural Products, Gangwon-do, 25451, Republic of Korea.
  • 6. Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea.
  • 7. Synovizen Inc, Seoul, 06621, Republic of Korea.
  • 8. Laboratory of mucosal immunology, Department of Biomedical Science, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea.
  • 9. East-West Medical Research Institute, Medical Science Research Institute, Kyung Hee University, Seoul, 02447, Republic of Korea.
  • 10. Department of Physical Education, College of Education, Daegu Catholic University, Gyeongsan, 38430, Republic of Korea.
  • 11. Department of Anatomy, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. [email protected].
  • 12. Department of Life Science, Chung-Ang University, Seoul, 06974, Republic of Korea. [email protected].
  • 13. Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon, 16499, Republic of Korea. [email protected].
  • 14. Department of Pharmacology, Ajou University School of Medicine, Suwon, 16499, Republic of Korea. [email protected].
  • 15. CIRNO, Sungkyunkwan University, Suwon, 16419, Republic of Korea. [email protected].
  • # Contributed equally.
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-1β, IL-6, and TNF-α secretion and markedly downregulated AD-related cytokines including IL-4, IL-5, IL-6, IL-13, IL-17, IFN-γ, TNF-α, and Tslp through regulation of NF-κB in ear tissue. Additionally, in vitro assessment of Treg differentiation revealed that 3'-SL directly induced TGF-β-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.

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