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Published on: September 22, 2019
Suppression of inflammation by recombinant Salmonella typhimurium harboring CCL22 microRNA
Won Suck Yoon1, Seung Rel Ryu, Seung Seok Lee
1Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Korea. biokorea@korea.ac.kr
Abstract:
Atopic dermatitis (AD) is an inflammatory, chronically relapsing, puritic skin disorder. These syndromes result from multifactorial inheritance, with interaction between genetic and environmental factors. In particular, the macrophage-derived chemokine CCL22 is directly implicated in skin inflammatory reactions and its levels are significantly elevated in serum and correlated with disease severity in AD. We tested the suppression of the CCL22 gene by microRNA (miRNA) and observed the effects in mice with inflammation similar to AD. We used Salmonella as a vector to deliver miRNA. The recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) was prepared for in vivo knockdown of CCL22. ST-miRCCL22 was orally inoculated into mice and the CCL22 gene suppressed with CCL22 miRNA in the activated lymphocytes. IgE and interleukin-4 were inhibited and interferon-γ was induced after treatments with ST-miRCCL22 and CCL22 was suppressed. Further, Th17 cells were suppressed in the atopic mice treated with ST-miRCCL22. These results suggested that suppression of the CCL22 gene using Salmonella induced anti-inflammatory effects.
Insights
This study shows that suppressing the CCL22 gene with microRNA delivered by Salmonella in mice with atopic dermatitis (AD) reduced inflammation. This approach offers a potential new therapy for AD by targeting key inflammatory pathways.
Area of Science:
- Immunology
- Genetics
- Microbiology
Background:
- Atopic dermatitis (AD) is a chronic inflammatory skin condition influenced by genetic and environmental factors.
- Elevated levels of the chemokine CCL22 are linked to AD severity.
- CCL22 plays a significant role in skin inflammation.
Purpose of the Study:
- To investigate the potential of microRNA (miRNA)-mediated suppression of the CCL22 gene.
- To evaluate the therapeutic effects of targeting CCL22 in an AD-like mouse model.
Main Methods:
- Developed a recombinant Salmonella typhimurium strain (ST-miRCCL22) to deliver CCL22 miRNA.
- Administered ST-miRCCL22 orally to mice with AD-like inflammation for in vivo gene knockdown.
- Assessed changes in immune markers including IgE, interleukin-4, interferon-γ, and Th17 cells.
Main Results:
- Oral administration of ST-miRCCL22 successfully suppressed the CCL22 gene in activated lymphocytes.
- Treatment led to inhibition of IgE and interleukin-4, and induction of interferon-γ.
- A significant suppression of Th17 cells was observed in treated atopic mice.
Conclusions:
- Suppression of the CCL22 gene using Salmonella-delivered miRNA demonstrates anti-inflammatory effects in an AD model.
- This strategy highlights the therapeutic potential of targeting CCL22 for managing atopic dermatitis.
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