FcRn alleviates mycobacterium-induced lung injury by triggering YBX1-mediated autophagy

Area of Science:

• Immunology
• Cell Biology
• Infectious Diseases

Background:

• Neonatal Fc receptor (FcRn) is crucial for IgG homeostasis.
• The role of FcRn in tuberculosis pathogenesis remains largely unknown.
• Understanding FcRn's function in infectious diseases is gaining attention.

Purpose of the Study:

• To investigate the role of FcRn in regulating BCG infection-induced autophagy.
• To elucidate the molecular mechanisms by which FcRn influences autophagy during tuberculosis.
• To explore FcRn's protective effects against BCG-induced lung injury.

Main Methods:

• Utilized CRISPR/Cas9 for FCGRT knockout mice and small interfering RNA for FcRn knockdown cells.
• Assessed autophagy markers using transmission electron microscopy, flow cytometry, and western blot.
• Identified FcRn interacting proteins via immunoprecipitation and mass spectrometry.

Main Results:

• FcRn knockout mice exhibited increased lung injury and reduced autophagy markers post-BCG infection compared to wild-type.
• FcRn knockdown in macrophages suppressed BCG-induced autophagy by activating the PI3K/AKT/mTOR pathway.
• FcRn was found to interact with Y-box binding protein 1 (YBX1), promoting its nuclear translocation.

Conclusions:

• FcRn plays a protective role against BCG-induced lung injury.
• FcRn triggers YBX1-mediated autophagy and suppresses the PI3K/AKT/mTOR pathway.
• These findings offer novel insights into the immune function of FcRn in tuberculosis prevention and treatment.