Transgene expression in various organs post BM-HSC transplantation

Area of Science:

• Immunology
• Gene Therapy
• Cell Biology

Background:

• Hematopoietic stem cell (HSC) gene therapy is vital for genetic disorders.
• Invariant chain (Ii) is a key chaperone for MHC class II (MHCII) molecules.

Purpose of the Study:

• To track invariant chain (Ii) expression and function in antigen-presenting cells after gene therapy.
• To assess the impact of Ii delivery on MHCII abundance in different organs.

Main Methods:

• Utilized lentivirus vectors to deliver Ii and GFP reporter genes into murine bone marrow-derived hematopoietic stem cells (BM-HSC).
• Monitored Ii and GFP expression in B cells, macrophages, and dendritic cells (DCs) from spleen, pancreatic lymph nodes (PLN), bone marrow (BM), and blood.
• Assessed functional impact on MHCII abundance.

Main Results:

• Ii and GFP expression were detected across various cell types and organs.
• Ii levels correlated with GFP levels primarily in splenic macrophages, PLN monocytes, and blood monocyte precursors.
• Ii expression in PLN and spleen showed a greater effect on MHCII abundance compared to BM or blood.

Conclusions:

• Gene therapy outcomes depend on Ii expression levels, which vary significantly by cell type and organ location.
• Findings inform gene therapy strategies and the understanding of immune molecule development and function.