MiR-146a Promotes Tolerogenic Properties of Dendritic Cells and through Targeting Notch1 Signaling

Autor:	Yin-Yan Lai, Hao-Cheng Tang, Kaitian Chen, Geng Xu, Hong-Yan Jiang, Jing Zheng
Rok vydání:	2020
Předmět:	0301 basic medicine Ovalbumin Inflammatory response Immunology Biology T-Lymphocytes Regulatory 03 medical and health sciences Mice 0302 clinical medicine Hypersensitivity Immune Tolerance Animals Humans Notch1 signaling RNA Small Interfering Receptor Notch1 Cells Cultured Inflammation Mice Inbred BALB C Innate immune system Cell Differentiation General Medicine Dendritic Cells Allergens Cell biology Disease Models Animal MicroRNAs 030104 developmental biology 030220 oncology & carcinogenesis Signal Transduction
Zdroj:	Immunological investigations. 49(5)
ISSN:	1532-4311
Popis:	MiR-146a has been shown to negatively regulate innate immune, inflammatory response and antiviral pathway, however, its role in the tolerogenic responses remains largely unknown. This study aimed to investigate the role of miR-146a in the OVA-induced allergic inflammation of dendritic cells (DCs).Bone marrow-derived DCs (BMDCs) were treated with OVA (100 µg/ml) for 24 h. MiR-146a expressions were assessed by quantitative RT-PCR. BMDCs were transfected with miR-146a mimics or inhibitor. Cell surface markers were analyzed by flow cytometry. Cytokine levels were determined by ELISA assay. Mixed lymphocyte culture assay was adopted to assess CD4 + T-cell differentiation. The 3' UTR luciferase reporter assay was utilized to determine the miRNA target sequence.OVA treatment significantly up-regulated miR-146a in BMDCs in a dose- and time-dependent manner. In the OVA-treated DCs, overexpression of miR-146a (mimics transfection) down-regulated the surface markers (CD80, CD86) and increased production of anti-inflammatory cytokines TGF-β1 and IL-10 but decreased pro-inflammatory cytokine IL-12. MiR-146a overexpression promoted immature DC to induce regulatory T cells (Treg) differentiation. By contrast, transfection of miR-146a inhibitor into DC exhibited the opposite trends. Notch1 was a direct target of miR-146a, and Notch1 knock-down induced similar effects as miR-146a mimics transfection in BMDCs. Moreover, the effect of miR-146a inhibitor on OVA-induced DC was attenuated by Notch1 knock-down.miRNA-146a promoted tolerogenic properties of DCs, at least partially, through targeting Notch1 signaling.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::378fad80a29eecdc561930a6d1a1826b https://pubmed.ncbi.nlm.nih.gov/31957545 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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