Dataset Information

MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.

ABSTRACT:

Background

Allergic conjunctivitis (AC) is an inflammation caused by a hypersensitive immune reaction of conjunctiva to external allergens. The microRNA (miRNA) miR-146a has been reported to suppress the exacerbation of inflammation. However, the underlying influence and mechanism of miR-146a in AC has not been completely elucidated.

Methods

We first successfully established an AC mouse model and AC cell model. After each model was treated based on the experimental purposes, miR-146a, FOXP3, and homeodomain-interacting protein kinases 3 (HIPK3) expressions were estimated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). The levels of immunoglobulin E (IgE), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were assessed using enzyme-linked immunosorbent assay (ELISA) kits; the related proteins were analyzed by western blot, immunofluorescence, or immunohistochemistry (IHC) assays; the interaction between miR-146a and HIPK3 were validated by a dual-luciferase reporter gene assay; and the inflammatory infiltration was certified by hematoxylin and eosin (H&E) staining.

Results

Our results indicated that miR-146a and FOXP3 were downregulated in AC model mice. Meanwhile, miR-146a overexpression could upregulate FOXP3 and inhibit inflammatory response in TGF-β-induced thymocytes. Besides, our results testified that HIPK3, as a target gene of miR-146a, could reverse miR-146a-mediated FOXP3 upregulation and inflammation inhibition. Moreover, we discovered that miR-146a could downregulate p-STAT3 by targeting HIPK3, and activation of STAT3 also could reverse miR-146a-mediated inflammation suppression in TGF-β-induced thymocytes. More importantly, miR-146a could ameliorate inflammatory infiltration and downregulate HIPK3 and p-STAT3 in AC model mice.

Conclusions

We demonstrated a possible protective mechanism by the miR-146a/HIPK3/STAT3 axis, by which decrease of miR-146a could aggravate the inflammation of AC.

SUBMITTER: Guo H

PROVIDER: S-EPMC9011242 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.

Guo Hui H Zhang Yongxin Y Liao Zifang Z Zhan Wenzhu W Wang Yuan Y Peng Yun Y Yang Meina M Ma Xudai X Yin Guogan G Ye Lin L

Annals of translational medicine 20220301 6

<h4>Background</h4>Allergic conjunctivitis (AC) is an inflammation caused by a hypersensitive immune reaction of conjunctiva to external allergens. The microRNA (miRNA) miR-146a has been reported to suppress the exacerbation of inflammation. However, the underlying influence and mechanism of miR-146a in AC has not been completely elucidated.<h4>Methods</h4>We first successfully established an AC mouse model and AC cell model. After each model was treated based on the experimental purposes, miR-1 ...[more]

PMID: 35434020

Similar Datasets

Project description:BackgroundThe recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.Methodology/principal findingsWe compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.Conclusion/significanceT. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.

Dataset Information

MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.

Background

Methods

Results

Conclusions

Publications

MiR-146a upregulates FOXP3 and suppresses inflammation by targeting HIPK3/STAT3 in allergic conjunctivitis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets