Human monocytes and macrophages regulate immune tolerance via integrin αvβ8-mediated TGFβ activation

Area of Science:

• Immunology
• Cell Biology

Background:

• Monocytes are key immune cells regulating inflammation through direct action or differentiation into macrophages.
• Understanding monocyte function control in health and disease remains incomplete.

Purpose of the Study:

• To investigate the mechanisms controlling human monocyte inflammatory responses.
• To identify pathways regulating monocyte and macrophage function in human tissues.

Main Methods:

• Analysis of human blood monocyte subsets (CD14+ and CD16+).
• Assessment of integrin αvβ8 and matrix metalloproteinase 14 expression.
• Measurement of TGFβ activation and TNFα production in response to LPS.
• Examination of monocyte-derived macrophage phenotypes.
• Evaluation of integrin αvβ8 expression in healthy and inflamed human intestine.

Main Results:

• Human CD14+ monocytes, unlike CD16+ monocytes, activate TGFβ via integrin αvβ8 and MMP14, suppressing TNFα production.
• TGFβ activation ability is maintained in anti-inflammatory macrophages but reduced in pro-inflammatory macrophages.
• Integrin αvβ8 is highly expressed on intestinal macrophages in health but significantly reduced in active inflammatory bowel disease.

Conclusions:

• Integrin αvβ8-mediated TGFβ activation is a critical regulator of human monocyte inflammatory responses.
• This pathway influences intestinal macrophage homeostasis and is dysregulated in inflammatory bowel disease.