Hypersensitivity pneumonitis onset and severity is regulated by CD103 dendritic cell expression

Area of Science:

• Immunology
• Pulmonology
• Cell Biology

Background:

• Pulmonary dendritic cells mediate lung responses to foreign antigens like Saccharopolyspora rectivirgula, a cause of hypersensitivity pneumonitis.
• Mechanisms of hypersensitivity pneumonitis onset and loss of homeostasis are unclear, potentially involving CD103+ dendritic cells.
• The regulatory role of CD103+ dendritic cells contrasts with their newly observed inflammatory potential, highlighting the need to understand CD103 modulation during inflammation.

Purpose of the Study:

• To investigate the role of CD103 expression in regulating hypersensitivity pneumonitis.
• To determine if CD103 on dendritic cells or T cells is critical for controlling airway inflammation.

Main Methods:

• Wild-type and CD103 knockout mice were intranasally exposed to S. rectivirgula to assess airway inflammation.
• Surface CD103 expression was analyzed post-exposure.
• Cell transfer experiments were conducted to ascertain the specific cell type (dendritic cells or T cells) requiring CD103 for immune regulation.

Main Results:

• Mice lacking CD103 exhibited a significantly heightened inflammatory response to S. rectivirgula exposure within 18 hours.
• CD103 expression on dendritic cells was rapidly reduced after S. rectivirgula exposure.
• Cell transfers confirmed that CD103 expression on dendritic cells, not T cells, is essential for controlling the initiation and intensity of hypersensitivity pneumonitis.

Conclusions:

• CD103 expression on dendritic cells is critical for maintaining immune homeostasis in the lungs.
• CD103 on dendritic cells, but not T cells, regulates the TH17-mediated airway inflammatory response in hypersensitivity pneumonitis.