Differential gene expression in thrombomodulin (TM; CD141)(+) and TM(-) dendritic cell subsets

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Thrombomodulin (TM) converts conventional dendritic cells (DCs) into tolerogenic DCs.
• TM(+) DCs are tolerogenic, while TM(-) DCs are pro-inflammatory.
• Previous studies showed TM's role in a mouse asthma model.

Purpose of the Study:

• To investigate how thrombomodulin treatment modulates inflammatory gene expression in dendritic cells.
• To analyze the molecular and functional differences between TM(+) and TM(-) DCs.

Main Methods:

• Murine bone marrow-derived DCs were treated with soluble thrombomodulin.
• Surface marker expression was analyzed.
• DCs were sorted into TM(+) and TM(-) populations for mRNA microarray analysis.
• Lipoxin production was measured by ELISA.
• Protein C activation and IL-10 antagonism were assessed.

Main Results:

• Thrombomodulin treatment reduced DC maturation markers and increased TM expression on DCs.
• TM(+) DCs showed reduced pro-inflammatory gene expression and increased cell cycle gene expression.
• TM(+) DCs exhibited increased 15-lipoxygenase expression and higher lipoxin production.
• IL-10 production was increased in TM(+) DCs, and its antagonism reversed TM's effects.
• TM(+) DCs supported protein C activation.

Conclusions:

• Thrombomodulin treatment generates tolerogenic TM(+) DCs with significantly altered gene expression profiles.
• TM(+) DCs exhibit reduced inflammatory potential and enhanced proliferative capacity.
• IL-10 plays a key mechanistic role in mediating thrombomodulin's effects on dendritic cells.
• Thrombomodulin-treated DCs offer a potential therapeutic strategy for immune modulation.