2'-fucosyllactose inhibits imiquimod-induced psoriasis in mice by regulating Th17 cell response via the STAT3 signaling pathway
| Autor: | Jonathan A. Lane, Daming Zuo, Liyun Zhang, Jiaqi Zeng, Lin Lin, Ledong Sun, Yao Li, Di Wang, Ke Lei |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
STAT3 Transcription Factor Immunology Anti-Inflammatory Agents chemical and pharmacologic phenomena Inflammation Imiquimod Pharmacology Stat3 Signaling Pathway 03 medical and health sciences 0302 clinical medicine Immune system RAR-related orphan receptor gamma Psoriasis medicine Immunology and Allergy Animals STAT3 Skin biology Chemistry Nuclear Receptor Subfamily 1 Group F Member 3 medicine.disease Mice Inbred C57BL 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Cytokines Th17 Cells Cytokine secretion Female medicine.symptom Trisaccharides medicine.drug Signal Transduction |
| Zdroj: | International immunopharmacology. 85 |
| ISSN: | 1878-1705 |
| Popis: | Psoriasis is a chronic immune-mediated inflammatory cutaneous disorder with Th17 cells and Th17-related cytokines playing an important role in its development. 2′-FL (2′-fucosyllactose), which makes up about 30% of all HMOs (human milk oligosaccharides) in blood type secretor positive maternal milk, plays an essential role in supporting aspects of immune development and regulation. To explore the immunomodulatory effect of 2′-FL in psoriasis, we employed the imiquimod (IMQ)-induced psoriasis-like mouse model. Our data showed that mice administered with 2′-FL exhibited attenuated skin damage and inflammation, characterized by significantly decreased erythema and thickness and reduced recruitment of pro-inflammatory cytokines, when compared to control mice. The alleviated skin inflammation in 2′-FL treated mice was associated with a reduced proportion of Th17 cells and decreased production of Th17-related cytokines. Furthermore, we have demonstrated that 2′-FL reduced the phosphorylation of STAT3 in the skin tissue from mice with IMQ stimulation, which could account for the decreasing recruitment of Th17 cells. In vitro studies showed that 2′-FL inhibited differentiation of Th17 cells, phosphorylation of STAT3, and RORγt mRNA levels in T cells under Th17 polarization. Our results indicate that 2′-FL ameliorates IMQ-induced psoriasis by inhibiting Th17 cell immune response and Th17-related cytokine secretion via modulation of the STAT3 signaling pathway. |
| Databáze: | OpenAIRE |
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