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Myd88 Signaling Is Involved in the Inflammatory Response in LPS-Induced Mouse Epididymitis and Bone-Marrow-Derived
Jin-Chuan Liu1,2, Peng Wang3, Qun-Xiong Zeng1,2
1Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518053, China.
International Journal of Molecular Sciences
|May 13, 2023
Summary
Myeloid differentiation primary response gene 88 (Myd88) on dendritic cells (DCs) drives inflammation in mouse epididymitis. Targeting Myd88 in DCs could offer new treatments for male infertility caused by immune dysfunction.
Area of Science:
- Immunology
- Reproductive Biology
- Cell Biology
Background:
- Epididymitis, an inflammation of the epididymis, is linked to male infertility.
- Dendritic cells (DCs) and myeloid differentiation primary response gene 88 (Myd88) are implicated in rodent epididymitis.
- The specific role of Myd88 in epididymal DCs during inflammation remains unclear.
Purpose of the Study:
- To investigate the function of Myd88 in dendritic cells (DCs) during epididymitis.
- To elucidate the Myd88 signaling pathway's involvement in DC subsets and cytokine production in an LPS-induced epididymitis model.
Main Methods:
- Lipopolysaccharide (LPS) was used to induce epididymitis in mice.
- CRISPR-Cas9 gene editing was employed to knock out Myd88 in bone-marrow-derived dendritic cells (BMDCs) and the DC2 cell line.
- In vivo and in vitro experiments assessed cytokine levels, gene expression, DC subset percentages, and cell apoptosis.
Main Results:
- LPS-induced epididymitis in mice showed elevated levels of pro-inflammatory cytokines (IL-1α, IL-6, IL-17A, TNF-α, IL-1β, MCP-1, GM-CSF) and Myd88-related gene mRNA.
- Monocyte-derived DC (Mo-DC) percentages increased in mice with epididymitis.
- In vitro, LPS increased BMDC apoptosis and inflammatory cytokine production, which were reduced after Myd88 knockout.
Conclusions:
- Myd88 signaling in dendritic cells plays a significant role in the inflammatory processes of mouse epididymitis.
- Targeting Myd88 on DCs presents a potential therapeutic strategy for immunological male infertility associated with epididymitis.
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