Matrix-producing neutrophils populate and shield the skin.

Area of Science:

• Immunology
• Cell Biology
• Tissue Engineering

Background:

• Physical barriers and innate immune cells are crucial for host defense against environmental threats.
• Innate immunity involves both chemical killing of pathogens and structural defense mechanisms.

Purpose of the Study:

• To investigate immune cell diversity across different tissues.
• To identify novel functions of neutrophils in skin immunity and barrier maintenance.

Main Methods:

• Analysis of neutrophil protein expression in naive skin.
• Investigating the role of matrix-producing neutrophils in skin structure and wound healing.
• Utilizing genetic manipulation to assess the impact of TGFβ signaling on neutrophil function in vivo.

Main Results:

• A distinct population of neutrophils in the skin expresses proteins for extracellular matrix (ECM) synthesis.
• These neutrophils contribute to ECM composition, mechanical properties, and barrier function in naive skin.
• Upon injury, these neutrophils form matrix 'rings' around wounds, preventing pathogen and foreign molecule entry.
• Impairment of TGFβ receptor signaling in neutrophils disrupted ring formation and increased bacterial invasion.

Conclusions:

• Neutrophils possess a previously unrecognized role in structural defense through ECM production.
• Matrix-producing neutrophils in the skin provide a physical shield against environmental threats.
• TGFβ signaling is essential for neutrophil-mediated wound matrix formation and host protection.